Systems, apparatuses, and methods for ventricular focal ablation

ABSTRACT

Systems, devices, and methods for electroporation ablation therapy are disclosed, with the system including a pulse waveform signal generator for medical ablation therapy, and an endocardial ablation device includes an inflatable member and at least one electrode for focal ablation pulse delivery to tissue. The signal generator may deliver voltage pulses to the ablation device in the form of a pulse waveform. The system may include a cardiac stimulator for generation of pacing signals and for sequenced delivery of pulse waveforms in synchrony with the pacing signal.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of International Patent ApplicationNo. PCT/US2018/050660, filed on Sep. 12, 2018, which claims priority toU.S. Provisional Application No. 62/557,390, filed on Sep. 12, 2017, thedisclosures of each of which are hereby incorporated by reference intheir entirety.

BACKGROUND

The generation of pulsed electric fields for tissue therapeutics hasmoved from the laboratory to clinical applications over the past twodecades, while the effects of brief pulses of high voltages and largeelectric fields on tissue have been investigated for the past fortyyears or more. Application of brief high DC voltages to tissue maygenerate locally high electric fields typically in the range of hundredsof volts per centimeter that disrupt cell membranes by generating poresin the cell membrane. While the precise mechanism of thiselectrically-driven pore generation or electroporation continues to bestudied, it is thought that the application of relatively brief andlarge electric fields generates instabilities in the lipid bilayers incell membranes, causing the occurrence of a distribution of local gapsor pores in the cell membrane. This electroporation may be irreversibleif the applied electric field at the membrane is larger than a thresholdvalue such that the pores do not close and remain open, therebypermitting exchange of biomolecular material across the membrane leadingto necrosis and/or apoptosis (cell death). Subsequently, the surroundingtissue may heal naturally.

While pulsed DC voltages may drive electroporation under the rightcircumstances, there remains an unmet need for thin, flexible,atraumatic devices that effectively deliver high DC voltageelectroporation ablation therapy selectively to endocardial tissue inregions of interest while minimizing damage to healthy tissue.

SUMMARY

Described here are systems, devices, and methods for ablating tissuethrough irreversible electroporation. Generally, an apparatus fordelivering a pulse waveform to tissue may include a catheter shaftdefining a longitudinal axis. An inflatable member may be coupled to adistal end of the catheter shaft. The inflatable member may have anouter surface including a set of electrically conductive portions. Afirst set of electrodes may be formed on a surface of the cathetershaft. A second set of electrodes may be formed distal to the first setof electrodes on the surface of the catheter shaft. The second set ofelectrodes may be electrically coupled to the outer surface of theinflatable member and electrically isolated from the first set ofelectrodes.

In some embodiments, an apparatus may include a catheter shaft defininga longitudinal axis. An inflatable member may be coupled to a distal endof the catheter shaft. A first set of electrodes may be formed on asurface of the catheter shaft. A second electrode may be formed on theinflatable member and electrically isolated from the first set ofelectrodes.

In some embodiments, an apparatus may include a catheter shaft defininga longitudinal axis. An inflatable member may be coupled to a distal endof the catheter shaft. A first set of electrodes may be formed on theinflatable member and disposed proximal to an equatorial plane of theinflatable member. A second set of electrodes may be formed on theinflatable member and disposed distal to the equatorial plane of theinflatable member. The second set of electrodes may be electricallyisolated from the first set of electrodes.

In some embodiments, a system may include a signal generator configuredfor generating a pulse waveform. An ablation device may be coupled tothe signal generator and configured for receiving the pulse waveform.The ablation device may be include a handle, a catheter shaft defining alongitudinal axis, and an inflatable member coupled to a distal end ofthe catheter shaft. The inflatable member may have an outer surfaceincluding a set of electrically conductive portions. A first set ofelectrodes may be formed on a surface of the catheter shaft. A secondset of electrodes may be formed distal to the first set of electrodes onthe surface of the catheter shaft. The second set of electrodes may beelectrically coupled to the outer surface of the inflatable member andelectrically isolated from the first set of electrodes.

In some embodiments, an apparatus may include a catheter shaft defininga longitudinal axis. An annular inflatable member may be coupled to adistal end of the catheter shaft. The inflatable member may define anannular inflatable member lumen therethrough. A first electrode may bedisposed on a distal end of the annular inflatable member. The firstelectrode may have a substantially planar portion. A second electrodemay extend from, and be distal to, the annular inflatable member lumenand be spaced apart from the first electrode.

In some embodiments, the first set of electrodes may have a polarityopposite to a polarity of the second set of electrodes during deliveryof a pulse waveform. In some embodiments, the first set of electrodesmay have a polarity opposite to the polarity of the second electrodeduring delivery of a pulse waveform. In some embodiments, the first setof electrodes may have a polarity opposite to the polarity of the secondset of electrodes during delivery of the pulse waveform.

In some embodiments, the catheter shaft may include a deflectableportion formed between the first set of electrodes and the second set ofelectrodes. The deflectable portion may be configured for deflecting aportion of the catheter including the second set of electrodes and theinflatable member up to about 210 degrees relative to the longitudinalaxis. In some embodiments, a fluid source may be coupled to theinflatable member and configured to inflate the inflatable member.

In some embodiments, one or more electrodes of the first set ofelectrodes and one or more electrodes of the second set of electrodesmay have an insulated electrical lead associated therewith, theinsulated electrical lead configured for sustaining a voltage potentialof at least about 700 V without dielectric breakdown of itscorresponding insulation, the insulated electrical lead disposed in alumen of the catheter shaft. In some embodiments, one or more electrodesof the first set of electrodes and the second electrode may have aninsulated electrical lead associated therewith, the insulated electricallead configured for sustaining a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation, theinsulated electrical lead disposed in a lumen of the catheter shaft.

In some embodiments, one or more electrodes of the first set ofelectrodes and one or more electrodes of the second set of electrodesmay be independently addressable. In some embodiments, one or moreelectrodes of the first set of electrodes and the second electrode maybe independently addressable.

In some embodiments, a distal-most electrode of the first set ofelectrodes may be spaced apart from a proximal most electrode of thesecond set of electrodes by between about 2 mm and about 10 mm. In someembodiments, a distal-most electrode of the first set of electrodes maybe spaced apart by at least about 5 mm from a proximal end of theinflatable member. In some embodiments, the first set of electrodes maybe formed on a portion of the catheter shaft having a length of betweenabout 1 mm and about 12 mm. In some embodiments, the inflatable memberhas a cross-sectional diameter in its equatorial plane of between about5 mm and about 15 mm. In some embodiments, the inflatable member mayhave a length of up to about 22 mm. In some embodiments, each electrodeof the first set of electrodes has a width of between about 1 mm andabout 5 mm and wherein adjacent electrodes of the first set ofelectrodes are spaced apart by between about 1 mm and about 5 mm.

In some embodiments, the inflatable member may have an asymmetric shapein a proximal-to-distal direction. In some embodiments, the inflatablemember may have a bulbous shape. In some embodiments, the inflatablemember may have a polyhedral shape. In some embodiments, a biocompatiblecoating may be formed on an outer surface of the inflatable member. Insome embodiments, the distal end of the catheter may extend into aninner volume of the inflatable member. In some embodiments, a set ofsplines may be coupled to the catheter and an inner surface of theinflatable member. The set of splines may be configured for translationalong the longitudinal axis to transition between a first configurationwhere the set of splines are approximately parallel to the longitudinalaxis and a second configuration where the set of splines bias away fromthe longitudinal axis.

In some embodiments, the pulse waveform may include a first level of ahierarchy of the pulse waveform in the form of a first set of pulses,each pulse having a pulse time duration, a first time intervalseparating successive pulses. A second level of the hierarchy of thepulse waveform includes a plurality of first sets of pulses as a secondset of pulses, a second time interval separating successive first setsof pulses, the second time interval being at least three times theduration of the first time interval. A third level of the hierarchy ofthe pulse waveform includes a plurality of second sets of pulses as athird set of pulses, a third time interval separating successive secondsets of pulses, the third time interval being at least thirty times theduration of the second level time interval. In some of theseembodiments, the pulse waveform includes a fourth level of the hierarchyof the pulse waveform includes a plurality of third sets of pulses as afourth set of pulses, a fourth time interval separating successive thirdsets of pulses, the fourth time interval being at least ten times theduration of the third level time interval.

In some embodiments, a distal portion of the catheter shaft furtherincludes a radiopaque portion. In some embodiments, the catheter shaftdefines a shaft lumen therethrough. In some embodiments, the first setof electrodes are formed on a distal portion of the catheter shaft.

In some embodiments, there are no electrodes formed on the outer surfaceof the inflatable member. In some embodiments, a conductive element maybe formed on a surface of the inflatable member. In some embodiments,the conductive element may include a set of spaced apart conductivestripes extending between ends of the inflatable member. In someembodiments, the conductive element may be electrically connected to thesecond set of electrodes. In some embodiments, each stripe of the set ofstripes may intersect at one or more of a proximal end and a distal endof the inflatable member.

In some embodiments, the conductive element may include an interlacedstructure defining a set of apertures. In some embodiments, a firstconductive element may be disposed on an outer surface of the inflatablemember and a second conductive element may be disposed on an innersurface of the inflatable member. The first conductive element may havean opposite polarity to the second conductive element during delivery ofa pulse waveform.

In some embodiments, a first conductive element may be disposed on anouter surface of the inflatable member and a second conductive elementmay be disposed on an inner surface of the inflatable member. The firstconductive element may have an opposite polarity to the secondconductive element during delivery of the pulse waveform.

In some embodiments, the first set of electrodes may be disposed on anouter surface of the catheter shaft and one or more electrodes of thesecond set of electrodes may be disposed on an inner surface of thecatheter shaft. In some embodiments, the second electrode may beconfigured to receive electrophysiology data. In some embodiments, thesecond electrode may be a distal electrode. In some embodiments, thesecond electrode may be the only electrode formed on the outer surfaceof the inflatable member.

In some embodiments, a distal end of the inflatable member may have aconcave surface facing away from a proximal end of the inflatablemember. In some embodiments, the inflatable member may have a set ofcurved faces. In some embodiments, at least one electrode of the secondset of electrodes is formed on one face of the inflatable member. Insome embodiments, one or more electrodes of the second set of electrodesmay be concave.

In some embodiments, the inflatable member may have a set of curvededges. In some embodiments, each electrode of the second set ofelectrodes may have a diameter of between about 3 mm and about 15 mm. Insome embodiments, a distal-most electrode of the first set of electrodesmay be spaced apart from a proximal end of the inflatable member by atleast about 3 mm. In some embodiments, the inflatable member wheninflated may have a cross-sectional diameter at its largest portion ofbetween about 6 mm and about 22 mm.

In some embodiments, the annular inflatable member when inflated mayhave a diameter of between about 10 mm and about 15 mm. In someembodiments, the second electrode may have a length of between about 2mm and about 10 mm. In some embodiments, the annular inflatable memberlumen may have a diameter of between about 4 mm and about 15 mm.

In some embodiments, a second set of electrodes may be formed on theinflatable member between the first set of electrodes and the secondelectrode. In some embodiments, the second electrode may beindependently addressable. In some embodiments, each electrode of thesecond set of electrodes may be independently addressable.

In some embodiments, the second set of electrodes may be formed on theinflatable member on an approximate plane approximately perpendicular tothe longitudinal axis. In some embodiments, each electrode of the secondset of electrodes may have a circular or elliptical shape. In someembodiments, a major axis of each electrode of the second set ofelectrodes having the elliptical shape may be substantially parallel tothe longitudinal axis.

In some embodiments, the second set of electrodes may include a distalelectrode formed at a distal end of the inflatable member. In someembodiments, each electrode of the second set of electrodes may have acircular or elliptical shape. In some embodiments, a major axis of eachelectrode of the second set of electrodes having the elliptical shapeexcept the distal electrode is substantially parallel to thelongitudinal axis.

In some embodiments, a method of focal ablation via irreversibleelectroporation includes the steps of advancing an ablation devicetowards an endocardial wall. The ablation device may include a cathetershaft defining a longitudinal axis and an inflatable member coupled to adistal end of the catheter shaft. The inflatable member may have anouter surface including a set of electrically conductive portions. Afirst set of electrodes may be formed on a surface of the cathetershaft. A second set of electrodes may be formed distal to the first setof electrodes on the surface of the catheter shaft. The second set ofelectrodes electrically may be coupled to the outer surface of theinflatable member and electrically isolated from the first set ofelectrodes. A pulse waveform may be generated. The pulse waveform may bedelivered to the endocardial wall via the ablation device.

In some embodiments, one of the first set of electrodes and the secondset of electrodes may be configured as anodes. The other of the firstset of electrodes and the second set of electrodes may be configured ascathodes. In some embodiments, the inflatable member of the ablationdevice may be transitioned from a first configuration to a secondconfiguration. In some embodiments, transitioning the inflatable memberfrom the first configuration to the second configuration includesinfusing the inflatable member with saline. In some embodiments, pulsedelectric field ablation energy may be delivered through the first set ofelectrodes and the second set of electrodes of the ablation device. Insome embodiments, the ablation device is configured to generate anelectric field intensity of between about 200 V/cm and about 800 V/cm.

In some embodiments, the ablation device may include a handle. Themethod may further include the steps of deflecting a portion of theablation device using the handle. In some embodiments, firstelectrophysiology data of the endocardial wall may be recorded. Secondelectrophysiology data of the endocardial wall may be recorded afterdelivering the pulse waveform. In some embodiments, the firstelectrophysiology data and the second electrophysiology data may includeintracardiac ECG signal data of the endocardial wall. In someembodiments, a diagnostic catheter may be advanced into the endocardialwall and recording the first electrophysiology data and the secondelectrophysiology data using the diagnostic catheter. In someembodiments, the first electrophysiology data and the secondelectrophysiology data may be recorded using the ablation device in thesecond configuration.

In some embodiments, the method may include the steps of creating atransseptal opening into a left atrium, advancing a guidewire and asheath into the left atrium through the transseptal opening, andadvancing the ablation device into a ventricle over the guidewire. Insome embodiments, the method may include the steps of creating a firstaccess site in a patient, advancing the guidewire through the firstaccess site and into a right atrium, advancing the dilator and a sheathover the guidewire and into the right atrium, advancing the dilator fromthe right atrium into the left atrium through an interatrial septum tocreate the transseptal opening, and dilating the transseptal openingusing the dilator. In some embodiments, a second access site may becreated in the patient for advancing a cardiac stimulator. In someembodiments, the method may include the steps of advancing the cardiacstimulator into a right ventricle, generating a pacing signal forcardiac stimulation of the heart using the cardiac stimulator, andapplying the pacing signal to the heart using the cardiac stimulator,the pulse waveform generated in synchronization with the pacing signal.

In some embodiments, the method may include the step of fluoroscopicallyimaging a radiopaque portion of the ablation device during one or moresteps. In some embodiments, the first access site is a femoral vein. Insome embodiments, the interatrial septum includes a fossa ovalis. Insome embodiments, the endocardial wall is a ventricle.

In some embodiments, the pulse waveform may include a first level of ahierarchy of the pulse waveform in the form of a first set of pulses,each pulse having a pulse time duration, a first time intervalseparating successive pulses. A second level of the hierarchy of thepulse waveform includes a plurality of first sets of pulses as a secondset of pulses, a second time interval separating successive first setsof pulses, the second time interval being at least three times theduration of the first time interval. A third level of the hierarchy ofthe pulse waveform includes a plurality of second sets of pulses as athird set of pulses, a third time interval separating successive secondsets of pulses, the third time interval being at least thirty times theduration of the second level time interval. In some of theseembodiments, the pulse waveform includes a fourth level of the hierarchyof the pulse waveform includes a plurality of third sets of pulses as afourth set of pulses, a fourth time interval separating successive thirdsets of pulses, the fourth time interval being at least ten times theduration of the third level time interval.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a block diagram of an electroporation system, according toembodiments.

FIGS. 2A-2D are side views of an ablation device in variousconfigurations, according to embodiments. FIG. 2A is a side view of anuninflated ablation device. FIG. 2B is a side view of an inflatedablation device. FIG. 2C is a side view of another embodiment of aninflated ablation device. FIG. 2D is a side view of another embodimentof an inflated ablation device.

FIG. 3 is a side view of an ablation device, according to otherembodiments.

FIGS. 4A-4B illustrates a method for tissue ablation, according toembodiments.

FIGS. 5A-5J are side and perspective views of ablation devices,according to other embodiments. FIG. 5A is a side view of an ablationdevice. FIG. 5B is a cross-sectional side view of the ablation devicedepicted in FIG. 5A. FIG. 5C is a cross-sectional side view of anotherembodiment of an ablation device. FIG. 5D is a perspective view of theablation device depicted in FIG. 5C. FIG. 5E is a cross-sectional sideview of the ablation device depicted in FIG. 5C. FIG. 5F is aperspective view of another embodiment of an ablation device. FIG. 5G isa perspective view of the ablation device depicted in FIG. 5F. FIG. 5His a perspective view of the ablation device depicted in FIG. 5F. FIG.5I is a perspective view of another embodiment of an ablation device.FIG. 5J is a cross-sectional side view of the ablation device depictedin FIG. 5I.

FIG. 6 is an example waveform showing a sequence of voltage pulses witha pulse width defined for each pulse, according to embodiments.

FIG. 7 schematically illustrates a hierarchy of pulses showing pulsewidths, intervals between pulses, and groupings of pulses, according toembodiments.

FIG. 8 provides a schematic illustration of a nested hierarchy ofmonophasic pulses displaying different levels of nested hierarchy,according to embodiments.

FIG. 9 is a schematic illustration of a nested hierarchy of biphasicpulses displaying different levels of nested hierarchy, according toembodiments.

FIG. 10 illustrates schematically a time sequence of electrocardiogramsand cardiac pacing signals together with atrial and ventricularrefractory time periods and indicating a time window for irreversibleelectroporation ablation, according to embodiments.

FIG. 11 is a side view of an ablation device, according to otherembodiments.

FIG. 12 is a side view of an ablation device, according to otherembodiments.

FIG. 13 is a side view of an ablation device, according to otherembodiments.

FIG. 14 is a side view of an ablation device, according to otherembodiments.

FIG. 15 is a side view of an ablation device, according to otherembodiments.

DETAILED DESCRIPTION

Described here are systems, devices, and methods for ablating tissuethrough irreversible electroporation. Generally, a system for deliveringa pulse waveform to tissue may include a signal generator configured forgenerating a pulse waveform and an ablation device coupled to the signalgenerator and configured to receive the pulse waveform. The ablationdevice may include a conductive inflatable member (e.g., balloon)coupled to a distal end of a catheter shaft for delivering energy toablate tissue by irreversible electroporation. A conductive metalpattern may be disposed on an outer surface of the inflatable member.One or more electrodes may be formed proximal to the inflatable memberon a surface of the catheter shaft. In some embodiments, the ablationdevice may be configured for delivering the pulse waveform to tissueduring use via one or more of the electrodes and inflatable member thatforms a bipole. In some embodiments, capacitive voltage delivery may beprovided using biphasic waveforms across a thickness of the inflatablemember wall. Embodiments of the ablation device described herein maydeliver energy to tissue sufficient for irreversible electroporationthrough the inflatable member of the ablation device that functions asan electrode. The inflatable member is inflatable so as to allow anelectric field and corresponding focal ablation lesions to be generated.In some embodiments, the ablation device may form focal ablation lesionsat a depth of between about 2 mm to about 15 mm or more that may besuitable to form wide and deep ablations in a ventricular wall.

In some embodiments, the ablation devices described herein may be usefulin treating ventricular arrhythmias (e.g., re-entrant ventriculartachycardia) that may occur in the ventricle and cause arrhythmia due tothe cardiac depolarization signal not completing a normal circuit, butrather, an alternative circuit such as looping back upon itself (e.g.,re-entrant circuit). For example, the ablation devices described hereinmay be used for scar homogenization or “debulking” that may ablate oneor more portions of scar tissue in order to electrically isolate and/ordestroy re-entrant circuits. The systems, devices, and methods describedherein may be used to create one or more focal ablation lesions using anendocardial approach, and in other embodiments, may be used in anepicardial approach.

In some embodiments, the ablation device may include one or moreelectrodes configured to receive ECG signals and used to generate ananatomical map of the patient. For example, an ECG recording electrodemay be disposed on one or more of the inflatable member and cathetershaft. This may allow the ablation device to both map and ablate tissue,thereby reducing cost, complexity, and procedure time when a separatemapping catheter is not used.

The systems, devices, and methods described herein may be used togenerate large electric field magnitudes at desired regions of interestto generate irreversible electroporation. An irreversibleelectroporation system as described herein may include a signalgenerator and a processor configured to apply one or more voltage pulsewaveforms to a selected set of electrodes and an inflatable member of anablation device to deliver energy to a region of interest (e.g.,ablation energy for a set of tissue in a ventricle). The pulse waveformsdisclosed herein may aid in therapeutic treatment of a variety ofcardiac arrhythmias (e.g., atrial fibrillation, re-entry ventriculararrhythmia, ventricular tachycardia, and/or the like). In order todeliver the pulse waveforms generated by the signal generator, one ormore electrodes of the ablation device may have an insulated electricallead configured for sustaining a voltage potential of at least about 700V without dielectric breakdown of its corresponding insulation. In someembodiments, at least some of the electrodes may be independentlyaddressable such that each electrode may be controlled (e.g., deliverenergy) independently of any other electrode of the device. In thismanner, the electrodes may deliver different energy waveforms withdifferent timing synergistically for electroporation of tissue.

The term “electroporation” as used herein refers to the application ofan electric field to a cell membrane to change the permeability of thecell membrane to the extracellular environment. The term “reversibleelectroporation” as used herein refers to the application of an electricfield to a cell membrane to temporarily change the permeability of thecell membrane to the extracellular environment. For example, a cellundergoing reversible electroporation can observe the temporary and/orintermittent formation of one or more pores in its cell membrane thatclose up upon removal of the electric field. The term “irreversibleelectroporation” as used herein refers to the application of an electricfield to a cell membrane to permanently change the permeability of thecell membrane to the extracellular environment. For example, a cellundergoing irreversible electroporation can observe the formation of oneor more pores in its cell membrane that persist upon removal of theelectric field.

Pulse waveforms for electroporation energy delivery as disclosed hereinmay enhance the safety, efficiency and effectiveness of energy deliveryto tissue by reducing the electric field threshold associated withirreversible electroporation, thus yielding more effective ablativelesions with a reduction in total energy delivered. In some embodiments,the voltage pulse waveforms disclosed herein may be hierarchical andhave a nested structure. For example, the pulse waveform may includehierarchical groupings of pulses having associated timescales. In someembodiments, the methods, systems, and devices disclosed herein maycomprise one or more of the methods, systems, and devices described inInternational Application Serial No. PCT/US2016/057664, filed on Oct.19, 2016, and titled “SYSTEMS, APPARATUSES AND METHODS FOR DELIVERY OFABLATIVE ENERGY TO TISSUE,” the contents of which are herebyincorporated by reference in its entirety.

In some embodiments, the systems may further include a cardiacstimulator used to synchronize the generation of the pulse waveform to apaced heartbeat. The cardiac stimulator may electrically pace the heartwith a cardiac stimulator and ensure pacing capture to establishperiodicity and predictability of the cardiac cycle. A time windowwithin a refractory period of the periodic cardiac cycle may be selectedfor voltage pulse waveform delivery. Thus, voltage pulse waveforms maybe delivered in the refractory period of the cardiac cycle so as toavoid disruption of the sinus rhythm of the heart. In some embodiments,an ablation device may include one or more catheters, guidewires,inflatable members, and electrodes. The ablation device may transforminto different configurations (e.g., deflated and inflated) to positionthe device within an endocardial space.

Generally, to ablate tissue, one or more catheters may be advanced in aminimally invasive fashion through vasculature to a target location. Themethods described here may include introducing a device into anendocardial space of the heart and disposing the device in contact witha ventricle or other cardiac surface. A pulse waveform may be generatedand delivered to one or more electrodes and a conductive inflatablemember of the device to ablate tissue. In some embodiments, the pulsewaveform may be generated in synchronization with a pacing signal of theheart to avoid disruption of the sinus rhythm of the heart. In someembodiments, the electrodes may be configured in anode-cathode subsets.The pulse waveform may include hierarchical waveforms to aid in tissueablation and reduce damage to healthy tissue.

I. Systems

Overview

Disclosed herein are systems and devices configured for tissue ablationvia the selective and rapid application of voltage pulse waveforms toaid tissue ablation, resulting in irreversible electroporation.Generally, a system for ablating tissue described here may include asignal generator and an ablation device having one or more electrodesand an inflatable member (e.g., balloon) for the selective and rapidapplication of DC voltage to drive electroporation. As described herein,the systems and devices may be deployed endocardially to treat cardiacarrhythmias. Voltage pulse waveforms may be applied to a subset of theelectrodes, with suitable anode/cathode electrode selections. A pacingsignal for cardiac stimulation may be generated and used to generate thepulse waveform by the signal generator in synchronization with thepacing signal.

Generally, the systems and devices described herein include one or morecatheters configured to ablate tissue in a ventricle of a heart. FIG. 1illustrates an ablation system (100) configured to deliver voltage pulsewaveforms. The system (100) may include an apparatus (120) including asignal generator (122), processor (124), memory (126), and cardiacstimulator (128). The apparatus (120) may be coupled to an ablationdevice (110), and optionally to a pacing device (130).

The signal generator (122) may be configured to generate pulse waveformsfor irreversible electroporation of tissue, such as, for example,ventricular tissue, such as that of the left ventricle. For example, thesignal generator (122) may be a voltage pulse waveform generator and beconfigured to deliver a pulse waveform to the ablation device (110). Thereturn electrode (140) in some embodiments may be coupled to a patient(e.g., disposed on a patient's back) to allow current to pass from theablation device (110) through the patient and then to the returnelectrode (140). In other embodiments, the return electrode (140) may bepart of the ablation device so that the electrode bipole is on thedevice. The processor (124) may incorporate data received from memory(126), cardiac stimulator (128), and pacing device (130) to determinethe parameters (e.g., amplitude, width, duty cycle, etc.) of the pulsewaveform to be generated by the signal generator (122). The memory (126)may further store instructions to cause the signal generator (122) toexecute modules, processes and/or functions associated with the system(100), such as pulse waveform generation and/or cardiac pacingsynchronization. For example, the memory (126) may be configured tostore pulse waveform and/or heart pacing data for pulse waveformgeneration and/or cardiac pacing, respectively.

In some embodiments, the ablation device (110) may include a catheterhaving an inflatable member (e.g., balloon) configured to deliver thepulse waveforms described in more detail below. In each of theembodiments described herein, the inflatable member may be inflatedusing gas, liquid, combinations thereof, and the like. For example, theablation device (110) may be introduced into an endocardial space andpositioned to align the inflatable member to a tissue surface, and thendeliver the pulse waveforms to ablate tissue. The ablation device (110)may include one or more electrodes (112), which may, in someembodiments, be independently addressable electrodes. Each electrode mayinclude an insulated electrical lead configured to sustain a voltagepotential of at least about 700 V without dielectric breakdown of itscorresponding insulation. In some embodiments, the insulation on each ofthe electrical leads may sustain an electrical potential difference ofbetween about 200 V to about 3,000 V across its thickness withoutdielectric breakdown. For example, the electrodes (112) may be groupedinto one or more anode-cathode subsets such as, for example, a subsetincluding one proximal electrode and one distal electrode. In someembodiments, the distal electrode may include at least a portion of aninflatable member. As used herein, proximal is towards a handle of anablation device and distal is towards a tip end of the ablation device.

When used, the pacing device (130) may be suitably coupled to thepatient (not shown) and configured to receive a heart pacing signalgenerated by the cardiac stimulator (128) of the apparatus (120) forcardiac stimulation. An indication of the pacing signal may betransmitted by the cardiac stimulator (128) to the signal generator(122). Based on the pacing signal, an indication of a voltage pulsewaveform may be selected, computed, and/or otherwise identified by theprocessor (124) and generated by the signal generator (122). In someembodiments, the signal generator (122) may be configured to generatethe pulse waveform in synchronization with the indication of the pacingsignal (e.g., within a common refractory window). For example, in someembodiments, the common refractory window may start substantiallyimmediately following a ventricular pacing signal (or after a very smalldelay) and last for a duration of approximately 250 ms or lessthereafter. In such embodiments, an entire pulse waveform may bedelivered within this duration.

The processor (124) may be any suitable processing device configured torun and/or execute a set of instructions or code. The processor may be,for example, a general purpose processor, a Field Programmable GateArray (FPGA), an Application Specific Integrated Circuit (ASIC), aDigital Signal Processor (DSP), and/or the like. The processor may beconfigured to run and/or execute application processes and/or othermodules, processes and/or functions associated with the system and/or anetwork associated therewith (not shown). The underlying devicetechnologies may be provided in a variety of component types, e.g.,metal-oxide semiconductor field-effect transistor (MOSFET) technologieslike complementary metal-oxide semiconductor (CMOS), bipolartechnologies like emitter-coupled logic (ECL), polymer technologies(e.g., silicon-conjugated polymer and metal-conjugated polymer-metalstructures), mixed analog and digital, and/or the like.

The memory (126) may include a database (not shown) and may be, forexample, a random access memory (RAM), a memory buffer, a hard drive, anerasable programmable read-only memory (EPROM), an electrically erasableread-only memory (EEPROM), a read-only memory (ROM), Flash memory, etc.The memory (126) may store instructions to cause the processor (124) toexecute modules, processes and/or functions associated with the system(100), such as pulse waveform generation and/or cardiac pacing.

The system (100) may be in communication with other devices (not shown)via, for example, one or more networks, each of which may be any type ofnetwork. A wireless network may refer to any type of digital networkthat is not connected by cables of any kind. However, a wireless networkmay connect to a wireline network in order to interface with theInternet, other carrier voice and data networks, business networks, andpersonal networks. A wireline network is typically carried over coppertwisted pair, coaxial cable or fiber optic cables. There are manydifferent types of wireline networks including, wide area networks(WAN), metropolitan area networks (MAN), local area networks (LAN),campus area networks (CAN), global area networks (GAN), like theInternet, and virtual private networks (VPN). Hereinafter, networkrefers to any combination of combined wireless, wireline, public andprivate data networks that are typically interconnected through theInternet, to provide a unified networking and information accesssolution.

Ablation Device

The systems described here may include one or more multi-electrodeablation devices configured to ablate tissue in a ventricle of a heartfor treating indications such as ventricular arrhythmia. FIG. 2A is aside view of an ablation device (200) (e.g., structurally and/orfunctionally similar to the ablation device (110)) including a cathetershaft (210) and an inflatable member (e.g., balloon) (240) coupled to adistal end of the catheter shaft (210). In some embodiments, theablation device (200) is useful for forming lesions on endocardialsurfaces via focal ablation, such as an inner surface of a ventricle, asdescribed herein. A distal portion of the inflatable member (240) mayinclude and/or be formed in an atraumatic shape that reduces trauma totissue (e.g., prevents and/or reduces the possibility of tissuepuncture). The catheter shaft (210) and inflatable member (240) may besized for advancement into an endocardial space (e.g., a leftventricle). The catheter shaft (210) may be flexible so as to bedeflectable, as shown and discussed in more detail with respect to FIG.3. Any of the catheter shafts described herein may include a shaft lumentherethrough. A set of electrical leads and/or a fluid (e.g., saline)may be disposed within the shaft lumen. The inflatable member (240) maybe configured to transition between a first configuration (e.g., adeflated state) and a second configuration (e.g., an inflated state). Inthe first configuration, the inflatable member (240) may have a diameterthat is about the same as a diameter of the catheter shaft (210) to aidin advancing the ablation device (200) through vasculature. For example,the inflatable member (240) in the first configuration may beapproximately parallel to a longitudinal axis (212) of the cathetershaft (210). For example, the inflatable member (240) may be in acompressed or crimped configuration. In the second configuration, theinflatable member (240) may have a cross-sectional diameter at itslargest portion (e.g., at its equatorial plane) in the range of betweenapproximately 5 mm and approximately 15 mm. For example, the inflatablemember (240) when inflated may bias away from the longitudinal axis. Theinflatable member (240), or a portion thereof, may include a conductiveouter surface (e.g., FIG. 2C) that may be configured as an anode orcathode for delivery of pulse waveform to tissue.

As shown in FIGS. 2A-2D, one or more electrodes (220, 230) may include aseries of metallic bands or rings disposed along a surface of a cathetershaft (210). For example, the ablation device (200) may comprise a firstset of electrodes (220) (e.g., one or more proximal electrodes) formedon a surface of a distal portion of the catheter shaft (210). In someembodiments, one or more electrodes (220, 230) may be formed on thecatheter shaft (210) along its entire circumference. In someembodiments, one or more electrodes (220, 230) may be formed on thesurface of a portion of a circumference of the catheter shaft (210). Forexample, electrode (220) may encircle the circumference of the cathetershaft (210). In some embodiments, one or more electrodes may be fullycovered by a thin layer of dielectric coating for biphasic operation.

In FIGS. 2A-2B, there are no electrodes formed on the outer surface ofthe inflatable member (240). In some embodiments, the ablation device(200) may comprise a second set of electrodes (230) (e.g., a singledistal electrode). The second set of electrodes (230) may be formeddistal to the first set of electrodes (210) on the surface of the distalportion of the catheter shaft (210). In some embodiments, the electrodes(220, 230) may be shaped to conform to the shape of the catheter shaft(210). For example, the electrodes may be press fit (e.g., crimped) tothe catheter shaft (210) or attached using a conductive adhesive. Thecatheter shaft (210) may include flexible portions (e.g., may bedeflectable) between the electrodes (220, 230) to enhance flexibilityand allow the device (200) to be deflected and aid in advancementthrough vasculature. In other embodiments, one or more electrodes (220,230) may include a helical winding to enhance flexibility.

Each of the electrodes of any of the ablation devices discussed hereinmay be connected to an insulated electrical lead (not shown) leading toa handle (not shown) coupled to a proximal portion of the catheter. Theinsulation on each of the electrical leads may sustain an electricalpotential difference of at least 700 V across its thickness withoutdielectric breakdown. In other embodiments, the insulation on each ofthe electrical leads may sustain an electrical potential difference ofbetween about 200 V to about 3,000 V across its thickness withoutdielectric breakdown, including all values and sub-ranges in between.This allows the electrodes and inflatable member coupled thereto toeffectively deliver electrical energy and to ablate tissue throughirreversible electroporation. The electrodes (220, 230) may, forexample, receive pulse waveforms generated by a signal generator (122)as discussed above with respect to FIG. 1.

The first set of electrodes (220) may be electrically coupled togetherusing one or more electrical leads. The second set of electrodes (230)may be electrically coupled together using a different set of electricalleads. An outer surface of the inflatable member (240) may include a setof electrically conductive portions and coupled to the second set ofelectrodes (230) and electrically isolated from the first set ofelectrodes (220). In some embodiments, the first set of electrodes (220)may be configured as an anode while the second set of electrodes (230)and inflatable member (240) may be configured as a cathode. Accordingly,a bipole may be formed between the first set of electrodes (220) and theinflatable member (240) that results in an electric field capable ofablating tissue (e.g., myocardial cells on an inner surface or within aventricle). The inflatable member (240) and the first set of electrodes(220) may be electrically isolated from each other. For example, thesecond set of electrodes (230) and the first set of electrodes (220) mayeach couple to a respective insulated electrical lead, with each leadhaving sufficient electrical insulation to sustain an electricalpotential difference of at least 700 V across its thickness withoutdielectric breakdown. In some embodiments, the first set of electrodes(220) may have an opposite polarity to the second set of electrodes(230) during delivery of a voltage pulse waveform.

The first and second sets of electrodes (220, 230) may include anatraumatic shape to reduce trauma to tissue. For example, the electrodes(220, 230) may have an atraumatic shape including a rounded, flat,curved, and/or blunted portion. For example, the electrodes (220, 230)in FIGS. 2A-2D may be ring electrodes. In some embodiments, the firstset of electrodes (220) may be located along any portion of the cathetershaft (210) proximal to the second set of electrodes (230). The secondset of electrodes (230) may be disposed on a surface of the cathetershaft (240) and/or flush with the surface of the inflatable member (240)so as to be electrically coupled to the inflatable member (240). Theelectrodes (220, 230) may have the same or different sizes, shapes,and/or location along the catheter shaft (210). The spacing betweenelectrodes of the first set of electrodes (220) may be configured toallow a distal portion of the catheter shaft (210) (e.g., deflectableportion) to deflect a predetermined amount (e.g., up to about 210degrees of deflection). For example, the deflectable portion may beconfigured for deflecting a portion of the catheter including the secondset of electrodes (230) and the inflatable member (240) up to about 210degrees relative to the longitudinal axis.

In some embodiments, the first set of electrodes (220) may includeelectrodes disposed along a portion of the catheter shaft (210) having alength between about 1 mm and about 12 mm from a proximal end to adistal end of the first set of electrodes (220). The first set ofelectrodes (220) may be spaced apart from each other and wired togethervia one or more insulated leads so as to function as a single electrode(e.g., anode or cathode) while allowing the catheter shaft (210) toremain flexible and facilitate deflection. In some embodiments, thefirst set of electrodes (220) may be spaced apart from the second set ofelectrodes (230) by a length of between about 2 mm and about 10 mm.

For each of the ablation devices discussed herein, the electrodes (220,230) may include biocompatible metals such as titanium, palladium, gold,silver, platinum or a platinum alloy. For example, the electrode maypreferably include platinum or a platinum alloy. In some embodiments,the proximal electrodes may have a biocompatible coating that permitscapacitive voltage delivery with biphasic waveforms. Each electrode(220, 230) may include an electrical lead having sufficient electricalinsulation to sustain an electrical potential difference of at least 700V across its thickness without dielectric breakdown. In otherembodiments, the insulation on each of the electrical leads may sustainan electrical potential difference of between about 200 V to about 3,000V across its thickness without dielectric breakdown, including allvalues and sub-ranges in between. The insulated electrical leads may runto the proximal handle portion of the ablation device (200) from wherethey may be connected to a suitable electrical connector. The cathetershaft (210) may be made of a flexible polymeric material such as Teflon,Nylon, Pebax, etc.

In some embodiments, one or more of the electrodes of the first andsecond sets of electrodes (220, 230) may be configured for receiving orsensing an ECG signal for recording electrophysiology data.Electrophysiology data may be used to generate an anatomical map thatmay be used to compare electrophysiology data recorded after energydelivery. The electrophysiology data may include intracardiac ECG signaldata. The ablation device (200) may include one or more ECG signalelectrodes. For example, one or more electrodes of the first set ofelectrodes (220) may be configured to receive an ECG signal. In someembodiments, an ECG signal electrode may be disposed on a surface of adistal end of an inflatable member (240) (not shown). The ECG signalelectrode may be coupled to its own insulated electrical lead. The ECGsignal electrode may be electrically isolated from the inflatable member(240) using, for example, a ring of insulation around the ECG signalelectrode electrically isolating the ECG signal electrode from theconductive inflatable member. In these embodiments, the ablation devicemay be used to record electrophysiology data in place of a mappingcatheter before and/or after tissue ablation. In some embodiments, theablation device (200) may include a location sensor that may generatelocation data of the ablation device disposed within vasculature. Theelectrophysiology data and location data may be used to generate ananatomical map of the electrophysiology data. In some embodiments, thelocation sensor may include an electromagnetic coil disposed at a distalend of the inflatable member (240). In other embodiments, the locationsensor may be disposed within a lumen of the catheter shaft (210).

In some embodiments, the inflatable member (240) may be coupled to thesecond set of electrodes (230), and configured to deliver a pulsewaveform from a signal generator to tissue during use. The inflatablemember (240) may be coupled to a distal portion of the catheter shaft(210) and configured to be conductive so as to function as one half ofan anode-cathode pair for delivery of irreversible electroporationenergy to tissue. The inflatable member (240) may be configured totransition between a first configuration (e.g., deflated inflatablemember in FIG. 2A) and a second configuration (e.g., inflated inflatablemember in FIGS. 2B-2D). The inflatable member (240) in the firstconfiguration may be in a compact, deflated state suitable foradvancement through vasculature. For example, the inflatable member(240) in the first configuration may be substantially empty of fluid,such as saline. The inflatable member (240) in the second configurationmay hold a predetermined volume of saline that fills and inflates theinflatable member (240) to a predetermined size and shape (e.g., havinga diameter to contact a diameter of a ventricle). The inflatable member(240) may transition to an intermediate configuration between the firstand second configuration as necessary, for example, to conform to alumen or advance the device through vasculature.

In some embodiments, the inflatable members as described herein may havean expandable structure and may be composed of materials including, butnot limited to polyvinyl chloride (PVC), polyethylene (PE), cross-linkedpolyethylene, polyolefins, polyolefin copolymer (POC), polyethyleneterephthalate (PET), nylon, polymer blends, polyester, polyimide,polyamides, polyurethane, silicone, polydimethylsiloxane (PDMS), and thelike. The inflatable member may be embedded with other materialsincluding, but not limited to metals, insulation, Kevlar, nylon fibers,and the like.

The distal portion of the inflatable member (240) disposed in a lumen(e.g., ventricle) may serve as a backstop to advancement of a distalportion of the catheter (200). By modifying a size of the inflatablemember (240) and manipulating the deflection of the catheter shaft(210), the inflatable member (240) may be positioned at a target tissuesite, such as, for example, near or in contact with the wall of a leftventricle. The distal portion of the catheter shaft (210) may include aset of electrodes (220, 230) (e.g., structurally and/or functionallysimilar to the electrode(s) (112)) where the inflatable member (240) maybe configured to contact an inner radial surface of a tissue lumen(e.g., ventricle). In some embodiments, a cross-sectional diameter ofthe inflatable member (240) at is largest portion (e.g., equatorialplane) when inflated may be between about 5 mm and about 15 mm. A lengthof the inflatable member (240) when inflated may be up to about 22 mm.In some embodiments, the length of the inflatable member (240) may besubstantially the same between the first and second configurations.

A proximal end of the inflatable member (240) may be coupled to asuitable electrical lead (e.g., via a second set of electrodes (230))and connected to the signal generator (122) of FIG. 1. The inflatablemember (240) may be configured as a cathode and the first set ofelectrodes (220) may be configured as an anode, or vice versa. In someembodiments, as described in detail herein, a set of proximal electrodes(220) and the inflatable member (240) may form a bipole. In this manner,the inflatable member (240) in the second configuration may be placedagainst, for example, an inner wall of the left ventricle in order todirectly generate localized or focal lesions thereupon by activation ofthe first and second set of electrodes (220, 230) using any suitablecombination of polarities. For example, the first and second set ofelectrodes (230, 240) may be configured with opposite polarities. Insome embodiments, the ablation device may be configured to generate anelectric field having an intensity of at least about 200 V/cm.

One or more of a biphasic signal may be applied to the bipole such thattissue may be ablated between the inflatable member (240) and the firstset of electrodes (220) at a desired location in the ventricle. Forexample, a biphasic pulse waveform may be delivered between the sets ofelectrodes of opposed polarities, resulting in a zone of irreversibleelectroporation ablation in the region around the inflatable member.

In some embodiments, the inflatable member (240) when inflated may beconfigured to contact endocardial tissue while the second set ofelectrodes (220) (also sometimes referred to as “proximal electrodes”)in the second configuration may not contact endocardial tissue. Theelectric field generated by the ablation device (200) due to conductionbetween the inflatable member (240) and proximal electrodes (220)through the blood pool and through tissue may result in focal ablationof tissue via irreversible electroporation.

In general, the inflatable member (240) when inflated may have anasymmetric shape in a proximal-to-distal direction, so that one end (forexample the distal end) of the inflatable member (240) is more bulbousthan the other end (for example the proximal end) of the inflatablemember (240). The inflatable member (240) when inflated may berotationally symmetric about the longitudinal axis of the catheter shaft(210). Such a bulbous distal portion can aid in positioning the device(200) in a ventricle as well as further controlling a size and depth offocal ablation. In this manner, the inflatable member (240) wheninflated may be placed against, for example, an endocardial surface suchas the inner surface of a ventricle in order to directly generatelesions thereupon by activation of appropriate electrodes (220, 230)using any suitable combination of polarities. For example, theinflatable member (240) may be placed at an endocardial surface and usedto form a lesion via focal ablation (e.g., a spot lesion).

In some embodiments, an outer surface of the inflatable member (240) mayinclude a set of conductive (e.g., metallized) portions. In thisconfiguration, a bipole may be formed between the outer surface of theinflatable member (240) and the first set of electrodes (220) (e.g.,proximal electrodes). For example, the outer surface of the inflatablemember (240) may include a deposition of a biocompatible metal material(e.g., gold, silver, platinum), metal plating, printed metalnanoparticle ink, and/or the like. A portion of the inflatable membermay include metal foil. The density of the metal material disposed onthe outer surface of the inflatable member (240) may be such as toensure electrical coupling with the second set of electrodes (230)(e.g., a distal ring electrode). The second set of electrodes (230) maybe electrically coupled to a set of electrically conductive portions ofthe outer surface of the inflatable member (240) such that theinflatable member (240) is electrically coupled to a respectiveelectrical lead. The electrode leads may be configured with sufficientinsulation and high dielectric strength to be suitable for delivery ofirreversible electroporation energy as described herein.

As shown in FIG. 2C, an ablation device (200′) may include a cathetershaft (210′) coupled at a distal end to an inflatable member (e.g.,balloon) (240′). A first set of electrodes (220′) and a second set ofelectrodes (230′) may be disposed on a surface of the catheter shaft(210′) and/or flush with the surface. In some embodiments, one or moreportions of the inflatable member (240′) may be conductive. For example,the entire outer surface of the inflatable member (240′) may beconductive or predetermined portions of the inflatable member (240′) maybe conductive and coupled to the second set of electrodes (230′). Asshown in FIG. 2C, the outer surface of the inflatable member may includeone more conductive elements (e.g., pattern) (242′) having a set ofspaced apart conductive stripes extending in a proximal-to-distaldirection between the ends of the inflatable member (240′). The one ormore conductive elements (242′) may be electrically isolated from eachother. The conductive stripes may be formed by techniques such as maskedelectrodeposition. In some embodiments, the conductive element (242′)may be disposed symmetrically on the inflatable member (240′). Each ofthe stripes of the conductive element (242′) may be electrically coupledto the distal electrode (230′). The stripes may intersect each other atproximal and distal ends of the inflatable member (240′) and/or betweenthe ends of the inflatable member (240′). The inflatable member (240′)may be flexible and/or expandable between the metal stripes of theconductive element (242′). The conductive element (242′) may be disposed(e.g., deposited) on the inflatable member (240′) in a manner thatmaintains electrical coupling with an electrical lead in the firstconfiguration, second configuration, and configurations in-between. Theconductive element (242′) may provide rigidity and/or stiffness to theinflatable member (240′) and aid in advancement of the inflatable member(240′) through vasculature. In some embodiments, the conductive element(242′) may include one or more spiral shaped metal portions. In someembodiments, the conductive element (242′) may include an interlacedstructure (e.g., mesh shape). For example, the interlaced structure mayform a set of polygonal apertures (e.g., openings) including one or moreof a circular shape, parallelogram, hexagonal, and the like.

As shown in FIG. 2D, an ablation device (200″) may include a cathetershaft (210″) coupled at a distal end to an inflatable member (e.g.,balloon) (240″). A first set of electrodes (220″) may be disposed on anouter surface of the catheter shaft (210″). A second set of electrodes(235″) may be disposed on an inner surface of the catheter shaft (210″).In some embodiments, one or more portions of the inflatable member(240″) may include a metal electrode portion (245″) (e.g., secondelectrode). In some embodiments, the second electrode (245″) is the onlyelectrode formed on the outer surface of the inflatable member. Aportion (245″) of the inflatable member surface (240″) may be metal. Forexample, a portion (245″) of the inflatable member (240″) may be adistal portion. In some embodiments, the inflatable member (240″) maydefine an inflatable member lumen (237″) extending along a firstlongitudinal axis of the catheter shaft (210″) to a distal end of theinflatable member (240″). A proximal end of an electrical lead (239″)may couple to the distal electrode (235″) and extend through theinflatable member lumen (237″) to couple to the electrode portion (245″)at a distal end of the inflatable member (240″). Accordingly, theelectrode portion (245″) may be configured to deliver irreversibleelectroporation voltage pulses. In some embodiments, the portion (245″)(e.g., formed of metal) of the inflatable member (240″) may beconfigured as an electrode of one polarity while the first set ofelectrodes (220″) (e.g., proximal electrode(s)) may be configured aselectrode(s) of the opposite polarity.

In some embodiments, a metallized outer surface of the inflatable memberas discussed herein may be further covered by a layer of biocompatiblematerial. The biocompatible coating may help prevent fibrin depositiondue to high voltage energy delivery to tissue by the ablation device. Inthis configuration, a bipole may be formed between the outer surface ofthe inflatable member and the first set of electrodes (e.g., proximalelectrode). However, the ablation device may be configured to deliverenergy using one or more biphasic waveforms capacitively across thebiocompatible coating on the inflatable member.

In some embodiments, the ablation device (200) may not include a secondset of electrodes (230) (e.g., distal electrode) disposed on an outersurface of the catheter shaft (210). Instead, the inflatable member(240) may be configured to include an inner and outer metallized surfacethat sandwiches the inflatable member (240). The inner and outermetallized surface may include any combination of conductive elements(242) described herein. An electrical lead may be directly connected tothe inner metallized surface of the inflatable member (240). In thisconfiguration, a bipole may be formed between the inflatable member(240) and the first set of electrodes (220).

Activation of the first and second sets of electrodes using apredetermined configuration of the inflatable member may providetargeted and precise focal ablation by controlling a focal ablation spotsize based on the expansion of the inflatable member. As describedherein, focal ablation of tissue may be used to treat ventriculararrhythmia. For example, when the inflatable member of the ablationdevice is partially filled with saline, a high intensity electric fieldhaving a relatively smaller/more focused diameter results in a focalablation lesion that is relatively smaller in diameter and shallower indepth. When the inflatable member of the ablation device is in thesecond configuration (e.g., full inflation state), a relatively largerand more dispersed electric field is generated, resulting in a focalablation lesion that is relatively wider and deeper. In this manner, byvarying the extent of expansion of the inflatable member, the depthand/or size of the lesion may be controlled with a single ablationdevice. Such aspects are useful for creating multiple lesions of varyingsizes and/or depths using the same ablation device. Saline may be usedto inflate the inflatable member and is not used for conduction. If theinflatable member (which is non-porous) is punctured or otherwisebreaks, the saline may safely leak out of the inflatable member.

In some embodiments, a distal end of the catheter shaft (210) may extendinto an internal cavity of the inflatable member (240) to providerigidity and support to a distal end of the ablation device (200) thatmay aid in advancement of the ablation device (200) through vasculature.The added rigidity may further provide additional tactile feedback to anoperator. For example, a distal end of the catheter shaft (210) coupledto a distal end of the inflatable member (240) may provide sufficientsupport and rigidity in advancing the inflatable member (240) through atransseptal puncture. In some embodiments, the distal end of thecatheter shaft (210) may include a set of splines within the inflatablemember that bias away from a longitudinal axis of the catheter shaft(210) and connect together at a distal end of the inflatable member(240). For example, the set of splines may be coupled to the cathetershaft (210) and an inner surface of the inflatable member (240) andconfigured for translation along the longitudinal axis to transitionbetween a first configuration where the set of splines are approximatelyparallel to the longitudinal axis and a second configuration where theset of splines bias away from the longitudinal axis. The set of splinesmay form a basket-like shape to provide rigidity and support to theinflatable member. In some embodiments, the distal end of the cathetershaft (210) may be configured with a predetermined stiffness differentfrom the stiffness of the catheter shaft (210) proximal to theinflatable member (240). For example, the distal end of the cathetershaft (210) within the inflatable member (240) may be stiffer thandeflectable portions of the catheter shaft (210).

In some embodiments, one or more distal portions of the catheter shaft(210) may include a radiopaque portion. For example, the distal portionof the catheter shaft (210) may include a radiopaque platinum coilwithin a cavity of the inflatable member (240). The radiopaque portionmay be fluoroscopically imaged to aid an operator in locating andpositioning the ablation device (200) within one or more body cavitiesof the patient. The radiopaque portion may include a set of markerbands. In some embodiments, one or more splines of the distal portion(e.g., distal end) of the catheter shaft (210) may include a radiopaqueportion (not shown) formed on a surface of that spline. Additionally oralternatively, a location sensor may be coupled to the distal end of thecatheter shaft (210) within the inflatable member (240).

FIG. 3 is a side view of another embodiment of an ablation device (300)(e.g., structurally and/or functionally similar to the ablation device(110, 200)) including a catheter shaft (310) having a first set ofelectrodes (320) provided proximal to a second set of electrodes (330)and an inflatable member (e.g., balloon) (340). The first set ofelectrodes may be formed on a surface of a distal portion of thecatheter shaft (310). During use, the electrodes (320, 330) may bedisposed in a ventricle in order to deliver a pulse waveform to ablatetissue (350), as described in more detail herein.

In some embodiments, a handle (not shown) may be coupled to a proximalportion of the ablation device (300) and may include a bending mechanism(e.g., one or more pull wires (not shown)) configured to modify theshape of the distal portion of the catheter shaft (310). For example,operation of a pull wire of the handle may increase or decrease acurvature in a deflectable portion (312) (e.g., bend in the cathetershaft (310)) in the distal portion of the catheter shaft (310). In someembodiments, the catheter (300) may have a deflectable portion (312)proximal to the second set of electrodes (330) and/or the first set ofelectrodes (320). The deflectable portion may be configured to deflectup to about 210 degrees relative to the longitudinal axis of thecatheter shaft (310). The curvature in the deflectable portion (312) ofthe catheter shaft (310) may be modified to allow the electrodes (320,330) and inflatable member (340) to be disposed near and/or in contactwith a tissue surface (350) (e.g., in contact with an inner radialsurface of a ventricle). In this manner, apposition of the ablationdevice (300) to tissue may be provided at a desired position andorientation (e.g., the inflatable member may be perpendicular, angled,or parallel to the tissue surface).

In some embodiments, the pulse waveform may be applied between the firstset of electrodes (320) and the inflatable member (340) configured inanode and cathode sets. It should be appreciated that any of the pulsewaveforms disclosed herein may be progressively or sequentially appliedto the set of anode-cathode pairs. In some embodiments, the first set ofelectrodes (320) may have an opposite polarity to the second set ofelectrodes (330) during delivery of a voltage pulse waveform. Theelectrodes (320, 330) may include a series of metallic bands or ringsand in some embodiments may be independently addressable. In someembodiments, the electrical leads of at least two electrodes of thefirst set of electrodes (320) may be electrically coupled at or near aproximal portion of the ablation device, such as, for example, withinthe handle.

FIG. 5A is a side view of an ablation device (500) (e.g., structurallyand/or functionally similar to the ablation device (110)) including acatheter shaft (510) and an inflatable member (e.g., balloon) (540)coupled to a distal end of the catheter shaft (510). In someembodiments, the ablation device (500) is useful for forming lesions onendocardial surfaces (555) via focal ablation. FIG. 5B illustratesspatial zones (530, 532) that may correspond to tissue ablation zones ofsufficiently high electric field intensities to generate focal ablationlesions on a tissue surface (555). As shown in FIG. 5A, the inflatablemember (540) may generally have a portion (545) that may be configuredas a second electrode and which may be at least partly metallic. In someembodiments, the first set of electrodes (520) of the ablation device(500) may be configured as cathodes and the second electrode (545) maybe configured as an anode, or vice versa. In some embodiments, the firstset of electrodes (520) may have an opposite polarity to the secondelectrode (545) during delivery of a voltage pulse waveform. The firstset of electrodes (520) may be formed on a surface of a distal portionof the catheter shaft (510). The flat distal second electrode (545) ofthe inflatable member (540) may be disposed against a tissue surface,such as a ventricular wall (555). The inflatable member (540) in thesecond configuration may have a circular cross-section. For example, theinflatable member (545) may have a diameter of about 12 mm and a voltagepotential difference of about 2,000 V may be applied between the anode(520) and cathode (545) electrodes. In some embodiments, the first setof electrodes (520) may have a width of about 3 mm each and a separationof about 3 mm between adjacent electrodes. In some embodiments, the mostdistal electrode of the first set of electrodes (520) may be separatedfrom the inflatable member (540) by at least about 5 mm.

FIG. 5B illustrates first and second spatial zones (530, 532)corresponding to an electric field intensity of magnitude of at leastabout 460 V/cm when a potential difference of about 2,000 V is appliedbetween the anode (520) and cathode (545) electrodes with the distalflat electrode (545) disposed against the tissue wall (555). The secondspatial zone (532) overlapping the tissue wall (555) may have a depth ofabout 7 mm and a width of about 20 mm.

In some embodiments, an ablation device (500′) may include an inflatablemember (540′) having a distal portion having a concave surface facingaway from a proximal end of the inflatable member (540′). As shown inFIGS. 5C and 5D, an inflatable member (540′) may include a first curvedportion (544′) and a second curved portion (545′). The first curvedportion (544′) may include a portion of the inflatable member (540′)configured to be in contact with an endocardial surface (555′) as shownin FIG. 5E.

In some embodiments, for example as shown in FIG. 5C, the inflatablemember (540′) may include an inflatable member lumen (537′) extendingalong a first longitudinal axis of the catheter shaft (510′) from adistal end of the catheter shaft (510′) to a distal end of theinflatable member (540′). A proximal end of an electrical lead (539′)may couple to a second set of electrodes (535′) (e.g., distal electrode)and extend through the inflatable member lumen (537′) to couple to theelectrode portion (545′) at a distal end of the inflatable member(540′). Accordingly, the electrode portion (545′) may be configured todeliver irreversible electroporation voltage pulses. The first set ofelectrodes (520′) and the portion (545′) may be configured with oppositepolarities.

FIG. 5D is a perspective view of the inflatable member (540′) of FIG. 5Chaving a metallic concave portion (545′) covering substantially anentire distal surface of the inflatable member (540′). For example, theinflatable member (545′) may have a diameter of about 12 mm and, forexample, a voltage potential difference of about 2,000 V may be appliedbetween the inflatable member (545′) (e.g., anode) and the first set ofelectrodes (520′) (e.g., cathodes). In some embodiments, the first setof electrodes (520′) may have a width of about 3 mm and a separation ofabout 3 mm between them. The distal-most electrode of the first set ofelectrodes (520′) may be separated from the inflatable member (540′) byabout 5 mm. The first set of electrodes (520′) have a width of about 3mm and a separation of about 3 mm between them. The most distalelectrode of the first set of electrodes (520′) may have a separation ofabout 7 mm from the inflatable member (540′). These dimensions areprovided as examples for illustrative purposes only and other values maybe chosen for these as found convenient for the clinical application.

FIG. 5E illustrates first and second spatial zones (530′, 532′)corresponding to an electric field intensity sufficient to generatefocal ablation lesions. The second ablation zone (532′) may correspondto a tissue ablation zone when the inflatable member (540′) is disposedagainst the tissue wall (555′). In some embodiments, the second set ofelectrodes (535′) and portion (545′) (e.g., comprising metal) of theinflatable member (540′) may be configured as an electrode of onepolarity while the first set of electrodes (520′) (e.g., proximalelectrode(s)) may be configured as electrode(s) of the oppositepolarity. FIG. 5E illustrates first and second spatial zones (530′,532′) corresponding to an electric field intensity having a magnitude ofat least about 460 V/cm when a potential difference of about 2,000 V isapplied between the anode (520′) and cathode (545′) electrodes with thedistal curved electrode portion (545′) (e.g., concave) disposed againstthe tissue wall (555′). The second spatial zone (532′) overlapping thetissue wall (555′) may have a depth of about 5 mm and a width of about21 mm. In some variations, the second spatial zone (532′) may have adepth of up to about 10 mm and a width of up to about 30 mm.

FIGS. 5F and 5G illustrate an ablation device (500″) (e.g., structurallyand/or functionally similar to the ablation device (110)) including acatheter shaft (510″) and an inflatable member (540″) coupled to adistal end of the catheter shaft (510″). In some embodiments, theablation device (500″) is useful for forming lesions on endocardialsurfaces via focal ablations. In some embodiments, the inflatable member(540″) may have a multi-faceted shape. In some embodiments, themulti-faceted shape may generally be a polyhedral shape with one or moresecond electrodes (504″) disposed on portions of one or more faces(511″) of the polyhedron. A first set of electrodes (520″) may bedisposed on the catheter shaft (510″). The inflatable member (540″) maygenerally have one or more second electrode portions (504″) that may beconfigured as an electrode of the second set of electrodes and which mayinclude metal. The inflatable member (540″) in the second configurationmay have a polyhedron shape with one or more faces (511″). The secondelectrode portions (504″) may be electrically wired together to functionas a single electrode or wired separately as independent electrodes.FIG. 5F illustrates a dodecahedron-shaped inflatable member (540″)having second electrode portions (504″) on six of the faces (511″). Insome embodiments, the first set of electrodes (520″) may have anopposite polarity to the second electrode portions (504″) duringdelivery of a voltage pulse waveform. In some embodiments, one or morefaces (511″) of the polyhedron may have a curved face.

In some embodiments, one or more of the second electrode portions (504″)of the second set of electrodes may be configured to receive ECGsignals, as described herein. The strength and/or pattern of the ECGsignal received by the one or more second electrode portions (504″) maybe used to determine a level of contact each of the second electrodeportions (504″) has with tissue (e.g., cardiac chamber wall). A set ofthe second electrode portions (504″) may be selected using the ECGsignals to be configured as an anode or cathode. Thus, one or moresecond electrode portions (504″) disposed on corresponding faces (511″)of the inflatable member (540″) may be used for tissue ablation based onan ECG signal strength corresponding to tissue contact. In someembodiments, the edges of the faces (511″) (e.g., polyhedral surfaces)may be rounded so as to form a “soft” face.

In some embodiments, one or more of the second set of electrodes (504″)disposed on a face (511″) may include a concave curved shape (e.g., theelectrodes may be indented) such that those faces (511″) may form apocket configured to contact a tissue surface. The edges (515″) of thesefaces (511″) may have a higher stiffness than the faces (511″)themselves such that the inflatable member (540″) in the secondconfiguration may form a polyhedron shape having one or more indentedfaces (511″).

FIG. 5G is another perspective view of the ablation device (500″) havingan inflatable member (540″) having a generally polyhedron shape withmetallized electrodes (504″) disposed on a portion of one or more faces(511″, 512″, 513″, 514″) of the inflatable member (540″). In someembodiments, a catheter shaft (510″) may define a catheter shaft lumen(not shown) configured for saline infusion to inflate the inflatablemember (540″). Electrical leads may also be disposed within the cathetershaft lumen and configured to connect to the one or more electrodes(504″). Edges (515″) of the faces (511″, 512″, 513″, 514″) may berounded and have a higher stiffness than a surface of the face so as toform an indented face surface when in the second configuration. In someembodiments, the diameter of the inflatable member (540″) in the secondconfiguration may be between about 6 mm and about 22 mm. The first setof electrodes (520″) may be separated by at least about 3 mm or morefrom a proximal end of the inflatable member (540″). The metallizedelectrode portions (504″) may have a diameter between about 6 mm andabout 15 mm. In some embodiments, the edges (522′″) of one or more faces(511′″) of the inflatable member (540′″) may be curved. As shown in FIG.5H, one or more electrode portions (504′″) of the second set ofelectrodes may be disposed on a face (511′″) of the inflatable member(540′″). The curved edges (522′″) (e.g., polyhedral surface) may form asoft face (511′″).

FIG. 5I illustrates an ablation device (500″″) (e.g., structurallyand/or functionally similar to the ablation device (110)) including acatheter shaft (510″″) and an inflatable member (e.g., balloon) (540″″)coupled to a distal end of the catheter shaft (510″″). In someembodiments, the ablation device (500″″) is useful for forming lesionson endocardial surfaces via focal ablation. In some embodiments, theinflatable member (540″″) may define an annular inflatable member lumen(533″″) (e.g., having an annular shape) and include a distal face(545″″) with a first electrode portion. The distal face (545″″) may havea substantially planar portion. A second electrode (535″″) (e.g. needle)may be disposed within the inflatable member lumen (533″″) and mayextend out from, and distal to, the inflatable member lumen (533″″)along a longitudinal axis of the inflatable member (540″″). Theinflatable member (540″″) may have a flat distal face (545″″) that maybe metallized and configured as the first electrode. The annular spacedefined by the inflatable member lumen (533″″) may separate the secondelectrode (535″″) from the annular inflatable member (540″″) to preventflash arcing when the second electrode (535″″) and the first electrodeportion (545″″) are polarized with opposite electrical polarities. Forexample, the needle may have a length between about 8 mm and about 10mm. The inflatable member (540″″) may have a diameter of about 12 mm.The inflatable member lumen (533″″) may have a diameter between about 4mm and about 8 mm.

FIG. 5J illustrates a spatial zone (532″″) corresponding to an electricfield intensity of magnitude of at least about 460 V/cm when a potentialdifference of about 2,000 V is applied between the electrode (535″″) andelectrode portions (545″″) with the flat distal electrode (545″″)disposed against the tissue wall (555″″). The spatial zone (532″″)overlapping the tissue wall (555″″) may have a depth of about 10 mm anda width of about 14 mm.

FIG. 11 is a side view of another embodiment of an ablation device(1100) (e.g., structurally and/or functionally similar to the ablationdevice (110, 200, 300, 500, 500′, 500″, 500″″) including a cathetershaft (1110) having a first set of electrodes (1120) provided proximalto a second set of electrodes (1130, 1132) and an inflatable member(e.g., balloon) (1140). The first set of electrodes (1120) may be formedon a surface of a distal portion of the catheter shaft (1110). That is,the first set of electrodes (1120) may be formed on a surface of thedistal end of the catheter shaft (1110). The second set of electrodes(1130, 1132) may be formed on a surface of a distal end of theinflatable member (1140) and may be electrically isolated from the firstset of electrodes (1120). In some embodiments, a major axis (e.g.,longitudinal axis) of the second electrodes (1132) may be substantiallyparallel to the longitudinal axis of the catheter shaft (1110) and/orinflatable member (1140).

In some embodiments, the ablation device (1100) is useful for forminglesions on endocardial surfaces via focal ablation, such as an innersurface of a ventricle. During use, the electrodes (1120, 1130, 1132)may be disposed in a ventricle in order to deliver a pulse waveform toablate tissue, as described in more detail herein. A distal portion ofthe inflatable member (1140) may include and/or be formed in anatraumatic shape that reduces trauma to tissue (e.g., prevents and/orreduces the possibility of tissue puncture). The catheter shaft (1110)and inflatable member (1140) may be sized for advancement into anendocardial space (e.g., left ventricle). The catheter shaft (1110) maybe flexible so as to be deflectable. For example, a deflectable portionof the catheter shaft (1110) may be configured for deflecting a portionof the catheter (1100) including the second set of electrodes (1130,1132) and the inflatable member (1140) up to about 210 degrees relativeto the longitudinal axis. The inflatable member (1140) may be configuredto transition between a first configuration (e.g., deflated state) and asecond configuration (e.g., inflated state). In the first configuration,the inflatable member (1140) may have a diameter that is about the sameas a diameter of the catheter shaft (1110) to aid in advancing theablation device (1100) through vasculature. For example, the inflatablemember (1140) in the first configuration may be approximately parallelto a longitudinal axis of the catheter shaft (1110). The inflatablemember (1140) in the second configuration may bias away from thelongitudinal axis. The first set of electrodes (1120) may bestructurally and/or functionally similar to the electrodes (220, 230)described with respect to FIGS. 2A-2D.

The first set of electrodes (1120) may be electrically coupled togetherusing one or more electrical leads. The second set of electrodes (1130,1132) may be electrically coupled together using a different set ofelectrical leads. In some embodiments, the inflatable member (1140) maybe electrically coupled to the second set of electrodes (1130, 1132). Avoltage pulse waveform delivered between the first set of electrodes(1120) and the inflatable member (1140) electrically coupled to thesecond set of electrodes (1130, 1132) may be used to form a lesion viafocal ablation (e.g., a spot lesion) of a predetermined size and shape.In some embodiments, the first set of electrodes (1120) may beconfigured as an anode while the second set of electrodes (1130, 1132)and inflatable member (240) may be configured as a cathode, or viceversa. Accordingly, a bipole may be formed between the first set ofelectrodes (1120) and the inflatable member (1140) that results in anelectric field capable of ablating tissue (e.g., myocardial cells on aninner surface or within a ventricle). The inflatable member (1140) andthe first set of electrodes (1120) may be electrically isolated fromeach other. For example, the second set of electrodes (1130, 1132) andthe first set of electrodes (1120) may each couple to a respectiveinsulated electrical lead, with each lead having sufficient electricalinsulation to sustain an electrical potential difference of at least 700V across its thickness without dielectric breakdown.

The first and second sets of electrodes (1120, 1130, 1132) may includean atraumatic shape to reduce trauma to tissue. For example, the firstset of electrodes (1120) may be ring electrodes. In some embodiments,the first set of electrodes (1120) may be located along any portion ofthe catheter shaft (1110) proximal to the second set of electrodes(1130, 1132). The first set of electrodes (1120) may be spaced apartfrom each other and wired together via one or more insulated leads so asto function as a single electrode (e.g., anode or cathode) whileallowing the catheter shaft (1110) to remain flexible and facilitatedeflection. The second set of electrodes (1130, 1132) may be disposed ona surface of the inflatable member (1140) and/or flush with the surfaceof the inflatable member (1140) so as to be electrically coupled to theinflatable member (1140). The second set of electrodes (1130, 1132) mayhave the same or different sizes, shapes, and/or location along theinflatable member (1140).

For example, the second set of electrodes (1130, 1132) may include adistal tip electrode (1130) and a set of generally circular orelliptically-shaped electrodes (1132) disposed around a circumference ofthe inflatable member (1140). For example, the second set of electrodes(1130) may be formed on the inflatable member (1140) on an approximateplane approximately perpendicular to the longitudinal axis. In someembodiments, each electrode of the second set of electrodes (1130, 1132)may be wired together. In other embodiments, subsets of the electrodesof the second set of electrodes (1130, 1132) may be electrically wiredtogether while other subsets may be independently addressable. In someembodiments, the distal tip electrode (1132) may be electricallyisolated from the first set of electrodes (1120). In some embodiments,each electrode of the second set of electrodes (1130, 1132) may beindependently addressable. The distal tip electrode (1132) may be formedat a distal portion of the inflatable member (1440) and electricallyisolated from the first set of electrodes (1120). The distal tipelectrode (1132) may have a diameter in the range between about 3 mm andabout 10 mm

In some embodiments, one or more of the electrodes of the first andsecond sets of electrodes (1120, 1132) may be configured for receivingor sensing an ECG signal for recording electrophysiology data. Theablation device (1100) may include one or more ECG signal electrodes.For example, one or more electrodes of the second set of electrodes(1130, 1132) may be configured to receive an ECG signal. These ECGsignal electrodes, such as the distal tip electrode (1130), may becoupled to its own insulated electrical lead. The ECG signal electrodemay be electrically isolated from the inflatable member (1140) using,for example, a ring of insulation around the ECG signal electrode. Inthese embodiments, the ablation device may be used to recordelectrophysiology data in place of a mapping catheter before and/orafter tissue ablation.

One or more of a biphasic signal may be applied to the bipole such thattissue may be ablated between the inflatable member (1140) and the firstset of electrodes (1120) at a desired location in the ventricle. In someembodiments, the inflatable member (1140) in the second configurationmay be configured to contact endocardial tissue while the first set ofelectrodes (1130) in the second configuration may not contactendocardial tissue. The electric field generated by the ablation device(1100) due to conduction between the inflatable member (1140) and firstset of electrodes (1120) through the blood pool and through tissue mayresult in focal ablation of tissue via irreversible electroporation. Theinflatable member (1140) when inflated may have an asymmetric shape in aproximal-to-distal direction, so that one end (for example the distalend) of the inflatable member (1140) is more bulbous than the other end(for example the proximal end) of the inflatable member (1140). Theinflatable member (1140) when inflated may be rotationally symmetricabout the longitudinal axis of the catheter shaft (1110). In thisconfiguration, the inflatable member (1140) may be contacting anendocardial surface and used to form a lesion via focal ablation (e.g.,a spot lesion).

In some embodiments, the catheter shaft (1110) may include a deflectableportion between the first set of electrodes (1120) and the second set ofelectrodes (1130) in the same manner as illustrated in FIG. 3. Thedeflectable portion may be configured to deflect up to about 210 degreesrelative to the longitudinal axis of the catheter shaft (1110). In someembodiments, an actuator (e.g., fluid source) may be coupled to theinflatable member and configured to transition the inflatable memberbetween the first configuration (e.g., deflated state) and the secondconfiguration (e.g., inflated state) by, for example, using pressurizedsaline.

FIG. 12 is a side view of another embodiment of an ablation device(1200) (e.g., structurally and/or functionally similar to the ablationdevice (110, 200, 300, 500, 500′, 500″, 500″″, 1100) including acatheter shaft (1210) having a first set of electrodes (1220) providedproximal to a second set of electrodes (1230) and an inflatable member(e.g., balloon) (1240). The first set of electrodes (1220) may be formedon a surface of a distal portion of the catheter shaft (1210). That is,the first set of electrodes (1220) may be formed on a surface of thedistal end of the catheter shaft (1210). The second set of electrodes(1230) may be formed on a surface of a distal end of the inflatablemember (1240) and may be electrically isolated from the first set ofelectrodes (1220). In some embodiments, the ablation device (1200) isuseful for forming lesions on endocardial surfaces via focal ablation,such as an inner surface of a ventricle. During use, the electrodes(1220, 1230) may be disposed in a ventricle in order to deliver a pulsewaveform to ablate tissue, as described in more detail herein. A distalportion of the inflatable member (1240) may include and/or be formed inan atraumatic shape that reduces trauma to tissue. The catheter shaft(1210) and inflatable member (1240) may be sized for advancement into anendocardial space (e.g., left ventricle). The catheter shaft (1210) maybe flexible so as to be deflectable. For example, a deflectable portionof the catheter shaft (1210) may be configured for deflecting a portionof the catheter (1200) including the second set of electrodes (1230) andthe inflatable member (1240) up to about 210 degrees relative to thelongitudinal axis. The inflatable member (1240) may be configured totransition between a first configuration (e.g., deflated state) and asecond configuration (e.g., inflated state). In the first configuration,the inflatable member (1240) may have a diameter that is about the sameas a diameter of the catheter shaft (1210) to aid in advancing theablation device (1200) through vasculature. For example, the inflatablemember (1240) in the first configuration may be approximately parallelto a longitudinal axis of the catheter shaft (1210). The inflatablemember (1240) when inflated may bias away from the longitudinal axis.The first set of electrodes (1220) may be structurally and/orfunctionally similar to the electrodes (220, 230) described with respectto FIGS. 2A-2D.

The first set of electrodes (1220) may be electrically coupled togetherusing one or more electrical leads. One or more of the second set ofelectrodes (1230) may be electrically coupled together using a differentset of electrical leads. A voltage pulse waveform delivered between thefirst set of electrodes (1220) and the second set of electrodes (1230)may be used to form a lesion via focal ablation (e.g., a spot lesion) ofa predetermined size and shape. In some embodiments, the first set ofelectrodes (1220) may be configured as an anode while the second set ofelectrodes (1230) may be configured as a cathode, or vice versa.Accordingly, a bipole may be formed between the first set of electrodes(1220) and the second set of electrodes (1230) that results in anelectric field capable of ablating tissue (e.g., myocardial cells on aninner surface or within a ventricle). The second set of electrodes(1230) and the first set of electrodes (1220) may be electricallyisolated from each other. For example, the second set of electrodes(1230) and the first set of electrodes (1220) may each couple to arespective insulated electrical lead, with each lead having sufficientelectrical insulation to sustain an electrical potential difference ofat least 700 V across its thickness without dielectric breakdown.

The first and second sets of electrodes (1220, 1230) may include anatraumatic shape to reduce trauma to tissue. For example, the first setof electrodes (1220) may be ring electrodes. In some embodiments, thefirst set of electrodes (1220) may be located along any portion of thecatheter shaft (1210) proximal to the second set of electrodes (1230).The first set of electrodes (1220) may be spaced apart from each otherand wired together via one or more insulated leads so as to function asa single electrode (e.g., anode or cathode) while allowing the cathetershaft (1210) to remain flexible and facilitate deflection. The secondset of electrodes (1230) may be disposed on a surface of the inflatablemember (1240) and/or flush with the surface of the inflatable member(1240) so as to be electrically coupled to the inflatable member (1240).The second set of electrodes (1230) may have the same or differentsizes, shapes, and/or location along the inflatable member (1240).

For example, the second set of electrodes (1230) may include a set ofgenerally circular electrodes disposed around a circumference of theinflatable member (1240). In some embodiments, each electrode of thesecond set of electrodes (1230) may be wired together. In otherembodiments, subsets of the electrodes of the second set of electrodes(1230) may be electrically wired together while other subsets may beindependently addressable.

In some embodiments, one or more of the electrodes of the first andsecond sets of electrodes (1220) may be configured for receiving orsensing an ECG signal for recording electrophysiology data. The ablationdevice (1200) may include one or more ECG signal electrodes. Forexample, one or more electrodes of the second set of electrodes (1230)may be configured to receive an ECG signal. These ECG signal electrodesmay be coupled to their own insulated electrical lead. In theseembodiments, the ablation device may be used to record electrophysiologydata in place of a mapping catheter before and/or after tissue ablation.

One or more of a biphasic signal may be applied to the bipole formed bythe first set of electrodes (122) and the second sets of electrodes(1230) such that tissue distal to or around the inflatable member (1240)may be ablated at a desired location in the ventricle. For example, abiphasic pulse waveform may be delivered between the sets of electrodes,resulting in a zone of irreversible electroporation ablation in theregion around the inflatable member. The inflatable member (1240) wheninflated may have an asymmetric shape in a proximal-to-distal direction,so that one end (for example the distal end) of the inflatable member(1240) is more bulbous than the other end (for example the proximal end)of the inflatable member (1240). The inflatable member (1240) wheninflated may be rotationally symmetric about the longitudinal axis ofthe catheter shaft (1210). In this configuration, the inflatable member(1240) may be placed at an endocardial surface and used to form a lesionvia focal ablation (e.g., a spot lesion). The electrode leads may beconfigured with sufficient insulation and high dielectric strength to besuitable for delivery of irreversible electroporation energy asdescribed herein.

In some embodiments, the catheter shaft (1210) may include a deflectableportion between the first set of electrodes (1220) and the second set ofelectrodes (1230) in some embodiments, or proximal to the first set ofelectrodes (1220) in other embodiments. The deflectable portion may beconfigured to deflect up to about 210 degrees relative to thelongitudinal axis of the catheter shaft (1210). In some embodiments, anactuator (e.g., fluid source) may be coupled to the inflatable memberand configured to transition the inflatable member between the firstconfiguration (e.g., deflated state) and the second configuration (e.g.,inflated state) by, for example, using pressurized saline.

FIG. 13 is a side view of another embodiment of an ablation device(1300) (e.g., structurally and/or functionally similar to the ablationdevice (110, 200, 300, 500, 500′, 500″, 500″″, 1100, 1200) including acatheter shaft (1310) having a first set of electrodes (1320) providedproximal to a second set of electrodes (1330, 1332) and an inflatablemember (e.g., balloon) (1340). The first set of electrodes (1320) may beformed on a surface of a distal portion of the catheter shaft (1310).That is, the first set of electrodes (1320) may be formed on a surfaceof the distal end of the catheter shaft (1310). The second set ofelectrodes (1330, 1332) may be formed on a surface of a distal end ofthe inflatable member (1340) and may be electrically isolated from thefirst set of electrodes (1320). In some embodiments, a major axis (e.g.,longitudinal axis) of the second electrodes (1332) may be substantiallyparallel to the longitudinal axis of the catheter shaft (1310) and/orinflatable member (1340).

In some embodiments, the ablation device (1300) is useful for forminglesions on endocardial surfaces via focal ablation, such as an innersurface of a ventricle. During use, the electrodes (1320, 1330, 1332)may be disposed in a ventricle in order to deliver a pulse waveform toablate tissue, as described in more detail herein. A distal portion ofthe inflatable member (1340) may include and/or be formed in anatraumatic shape that reduces trauma to tissue. The catheter shaft(1310) and inflatable member (1340) may be sized for advancement into anendocardial space (e.g., left ventricle). The catheter shaft (1310) maybe flexible so as to be deflectable. For example, a deflectable portionof the catheter shaft (1310) may be configured for deflecting a portionof the catheter (1300) including the second set of electrodes (1330,1332) and the inflatable member (1340) up to about 210 degrees relativeto the longitudinal axis. The inflatable member (1340) may be configuredto transition between a first configuration (e.g., deflated state) and asecond configuration (e.g., inflated state). In the first configuration,the inflatable member (1340) may have a diameter that is about the sameas a diameter of the catheter shaft (1310) to aid in advancing theablation device (1300) through vasculature. For example, the inflatablemember (1340) in the first configuration may be approximately parallelto a longitudinal axis of the catheter shaft (1310). The inflatablemember (1340) when inflated may bias away from the longitudinal axis.The first set of electrodes (1320) may be structurally and/orfunctionally similar to the electrodes (220, 230) described with respectto FIGS. 2A-2D.

The first set of electrodes (1320) may be electrically coupled togetherusing one or more electrical leads. The second set of electrodes (1330,1332) may be electrically coupled together using a different set ofelectrical leads. A voltage pulse waveform delivered between the firstset of electrodes (1320) and the second set of electrodes (1330, 1332)to form a lesion via focal ablation (e.g., a spot lesion) of apredetermined size and shape. In some embodiments, the first set ofelectrodes (1320) may be configured as an anode while the second set ofelectrodes (1330, 1332) may be configured as a cathode, or vice versa.The second set of electrodes (1330, 1332) and the first set ofelectrodes (1320) may be electrically isolated from each other. Forexample, the second set of electrodes (1330, 1332) and the first set ofelectrodes (1320) may each couple to a respective insulated electricallead, with each lead having sufficient electrical insulation to sustainan electrical potential difference of at least 700 V across itsthickness without dielectric breakdown.

The first and second sets of electrodes (1320, 1330, 1332) may includean atraumatic shape to reduce trauma to tissue. For example, the firstset of electrodes (1320) may be ring electrodes. In some embodiments,the first set of electrodes (1320) may be located along any portion ofthe catheter shaft (1310) proximal to the second set of electrodes(1330, 1332). The first set of electrodes (1320) may be spaced apartfrom each other and wired together via one or more insulated leads so asto function as a single electrode (e.g., anode or cathode) whileallowing the catheter shaft (1310) to remain flexible and facilitatedeflection. The second set of electrodes (1330, 1332) may be disposed ona surface of the inflatable member (1340) and/or flush with the surfaceof the inflatable member (1340) so as to be electrically coupled to theinflatable member (1340). The second set of electrodes (1330, 1332) mayhave the same or different sizes, shapes, and/or location along theinflatable member (1340).

For example, the second set of electrodes (1330, 1332) may include adistal tip electrode (1330) and a set of generally elliptically-shapedelectrodes (1332) disposed around a circumference of the inflatablemember (1340). For example, the second set of electrodes (1330) may beformed on the inflatable member (1340) on an approximate planeapproximately perpendicular to the longitudinal axis. In someembodiments, a longitudinal axis of each of the electrodes (1332) may besubstantially parallel to the longitudinal axis of the catheter shaft(1310) and/or inflatable member (1340). In some embodiments, eachelectrode of the second set of electrodes (1330, 1332) may be wiredtogether. In other embodiments, subsets of the electrodes of the secondset of electrodes (1330, 1332) may be electrically wired together whileother subsets (e.g., the distal tip electrode) may be independentlyaddressable. In some embodiments, the distal tip electrode (1332) may beelectrically isolated from the first set of electrodes (1320). In someembodiments, each electrode of the second set of electrodes (1330, 1332)may be independently addressable. The distal tip electrode (1330) may beformed at a distal portion of the inflatable member (1340) andelectrically isolated from the first set of electrodes (1320).

In some embodiments, one or more of the electrodes of the first andsecond sets of electrodes (1320, 1330, 1332) may be configured forreceiving or sensing an ECG signal for recording electrophysiology data.The ablation device (1300) may include one or more ECG signalelectrodes. For example, one or more electrodes of the second set ofelectrodes (1330, 1332) may be configured to receive an ECG signal.These ECG signal electrodes, such as the distal tip electrode (1330),may be coupled to its own insulated electrical lead. In theseembodiments, the ablation device may be used to record electrophysiologydata in place of a mapping catheter before and/or after tissue ablation.

The inflatable member (1340) when inflated may have an asymmetric shapein a proximal-to-distal direction, so that one end (for example thedistal end) of the inflatable member (1340) is more bulbous than theother end (for example the proximal end) of the inflatable member(1340). The inflatable member (1340) when inflated may be rotationallysymmetric about the longitudinal axis of the catheter shaft (1310). Inthis configuration, the inflatable member (1340) may be placed at anendocardial surface and used to form a lesion via focal ablation (e.g.,a spot lesion). The electrode leads may be configured with sufficientinsulation and high dielectric strength to be suitable for delivery ofirreversible electroporation energy as described herein.

In some embodiments, the catheter shaft (1310) may include a deflectableportion between the first set of electrodes (1320) and the second set ofelectrodes (1330), or proximal to the first set of electrodes (1320).The deflectable portion may be configured to deflect up to about 210degrees relative to the longitudinal axis of the catheter shaft (1310).In some embodiments, an actuator (e.g., fluid source) may be coupled tothe inflatable member and configured to transition the inflatable memberbetween the first configuration (e.g., deflated state) and the secondconfiguration (e.g., inflated state) by, for example, using pressurizedsaline.

FIG. 14 is a side view of another embodiment of an ablation device(1400) (e.g., structurally and/or functionally similar to the ablationdevice (110, 200, 300, 500, 500′, 500″, 500″″, 1100, 1200, 1300)including a catheter shaft (1410) having a first set of electrodes(1420) provided proximal to a second set of electrodes (1430, 1432) andan inflatable member (e.g., balloon) (1440). The first set of electrodes(1420) may be formed on a surface of a proximal portion of theinflatable member (1440). For example, the first set of electrodes(1420) may be formed proximal to an equatorial plane of the inflatablemember (1440). As used herein, the equatorial plane of the inflatablemember (1440) refers to the plane intersecting the maximumcross-sectional diameter of the inflatable member (1440) when inflated.That is, a proximal portion of the inflatable member (1440) is proximalto a cross-sectional diameter of the inflatable member (1440) at itslargest portion. The second set of electrodes (1430, 1432) may be formedon a surface of the inflatable member (1440) distal to the equatorialplane and may be electrically isolated from the first set of electrodes(1420). In some embodiments, a major axis (e.g., longitudinal axis) ofthe first set of electrodes (1420) and the second set of electrodes(1432) may be substantially parallel to the longitudinal axis of thecatheter shaft (1410) and/or inflatable member (1440).

In some embodiments, the ablation device (1400) is useful for forminglesions on endocardial surfaces via focal ablation, such as an innersurface of a ventricle. During use, the electrodes (1420, 1430, 1432)may be disposed in a ventricle in order to deliver a pulse waveform toablate tissue, as described in more detail herein. A distal portion ofthe inflatable member (1440) may include and/or be formed in anatraumatic shape that reduces trauma to tissue. The catheter shaft(1410) and inflatable member (1440) may be sized for advancement into anendocardial space (e.g., left ventricle). The catheter shaft (1410) maybe flexible so as to be deflectable. For example, a deflectable portionof the catheter shaft (1410) may be configured for deflecting a portionof the catheter (1400) including first set of electrodes (1420) and thesecond set of electrodes (1430, 1432) and the inflatable member (1440)up to about 210 degrees relative to the longitudinal axis. Theinflatable member (1440) may be configured to transition between a firstconfiguration (e.g., deflated state) and a second configuration (e.g.,inflated state). In the first configuration, the inflatable member(1440) may have a diameter that is about the same as a diameter of thecatheter shaft (1410) to aid in advancing the ablation device (1400)through vasculature. For example, the inflatable member (1440) in thefirst configuration may be approximately parallel to a longitudinal axisof the catheter shaft (1410). The inflatable member (1440) when inflatedmay bias away from the longitudinal axis.

The first set of electrodes (1420) may be electrically coupled togetherusing one or more electrical leads. The second set of electrodes (1430,1432) may be electrically coupled together using a different set ofelectrical leads Accordingly, a bipole may be formed between the firstset of electrodes (1420) and the second set of electrodes (1430, 1432)that results in an electric field capable of ablating tissue (e.g.,myocardial cells on an inner surface or within a ventricle). Forexample, the second set of electrodes (1430, 1432) and the first set ofelectrodes (1420) may each couple to a respective insulated electricallead, with each lead having sufficient electrical insulation to sustainan electrical potential difference of at least 700 V across itsthickness without dielectric breakdown.

The first and second sets of electrodes (1420, 1430, 1432) may includean atraumatic shape to reduce trauma to tissue. For example, the firstset of electrodes (1420) may have a set of generally elliptically-shapedelectrodes (1420) disposed around a circumference of the inflatablemember (1440) In some embodiments, the first set of electrodes (1420)may be located along any portion of the inflatable member (1440)proximal to the second set of electrodes (1430, 1432). The first set ofelectrodes (1420) may be spaced apart from each other and wired togethervia one or more insulated leads so as to function as a single electrode(e.g., anode or cathode). The second set of electrodes (1430, 1432) maybe disposed on a distal end of the inflatable member (1430, 1432) andelectrically isolated from the first set of electrodes (1420).

The first and second set of electrodes (1420, 1430, 1432) may have thesame or different sizes, shapes, and/or location along the inflatablemember (1440). For example, one or more electrodes of the first andsecond set of electrodes (1420, 1430, 1432) may have a generallyelliptical shape. For example, the second set of electrodes (1430, 1432)may include a distal tip electrode (1430) and a set of generallyelliptically-shaped electrodes (1432) disposed around a circumference ofthe inflatable member (1440). In some embodiments, a longitudinal axisof each of the electrodes (1420, 1432) may be substantially parallel tothe longitudinal axis of the catheter shaft (1410) and/or inflatablemember (1440). In some embodiments, each electrode of the second set ofelectrodes (1430, 1432) may be wired together. In other embodiments,subsets of the electrodes of the second set of electrodes (1430, 1432)may be electrically wired together while other subsets (e.g., the distaltip electrode) may be independently addressable. In some embodiments,the distal tip electrode (1432) may be electrically isolated from thefirst set of electrodes (1420). In some embodiments, one or moreelectrodes of the first and second set of electrodes (1420, 1430, 1432)may be independently addressable. The distal tip electrode (1430) may beformed at a distal portion of the inflatable member (1440).

In some embodiments, one or more of the electrodes of the first andsecond sets of electrodes (1420, 1430, 1432) may be configured forreceiving or sensing an ECG signal for recording electrophysiology data.The ablation device (1400) may include one or more ECG signalelectrodes. For example, one or more electrodes of the second set ofelectrodes (1430, 1432) may be configured to receive an ECG signal.These ECG signal electrodes, such as the distal tip electrode (1430),may be coupled to its own insulated electrical lead. In theseembodiments, the ablation device may be used to record electrophysiologydata in place of a mapping catheter before and/or after tissue ablation.

In some embodiments, the first and second set of electrodes (1420, 1430,1432) may be configured to deliver a pulse waveform from a signalgenerator to tissue during use. The inflatable member (1440) may becoupled to a distal portion of the catheter shaft (1410) and configuredfor delivery of irreversible electroporation energy to tissue. The firstset of electrodes (1420) and the second set of electrodes (1430, 1432)may have opposite electrical polarities during delivery of a pulsewaveform.

The electric field generated by the ablation device (1400) due toconduction between the second set of electrodes (1430, 1432) and thefirst set of electrodes (1420) through the blood pool and through tissuemay result in focal ablation of tissue via irreversible electroporation.The inflatable member (1440) when inflated may have an asymmetric shapein a proximal-to-distal direction, so that one end (for example thedistal end) of the inflatable member (1440) is more bulbous than theother end (for example the proximal end) of the inflatable member(1440). The inflatable member (1440) when inflated may be rotationallysymmetric about the longitudinal axis of the catheter shaft (1410). Inthis configuration, the inflatable member (1440) may be placed at anendocardial surface and used to form a lesion via focal ablation (e.g.,a spot lesion). The electrode leads may be configured with sufficientinsulation and high dielectric strength to be suitable for delivery ofirreversible electroporation energy as described herein.

In some embodiments, the catheter shaft (1410) may include a deflectableportion such as in a distal portion of the catheter shaft (1410). Thedeflectable portion may be configured to deflect up to about 210 degreesrelative to the longitudinal axis of the catheter shaft (1410). In someembodiments, an actuator (e.g., fluid source) may be coupled to theinflatable member and configured to transition the inflatable memberbetween the first configuration (e.g., deflated state) and the secondconfiguration (e.g., inflated state) by, for example, using pressurizedsaline.

FIG. 15 is a side view of another embodiment of an ablation device(1500) (e.g., structurally and/or functionally similar to the ablationdevice (110, 200, 300, 500, 500′, 500″, 500″″, 1100, 1200, 1300, 1400)including a catheter shaft (1510) having a first set of electrodes(1520) provided proximal to a second set of electrodes (1530, 1532,1534) and an inflatable member (e.g., balloon) (1540). The first set ofelectrodes (1510) may be formed on a surface of a distal portion of thecatheter shaft (1510). That is, the first set of electrodes (1520) maybe formed on a surface of the distal end of the catheter shaft (1510).The second set of electrodes (1530, 1532, 1534) may be formed on asurface of the inflatable member (1540) and may be electrically isolatedfrom the first set of electrodes (1520). In some embodiments, a majoraxis (e.g., longitudinal axis) of the second electrodes (1532, 1534) maybe substantially parallel to the longitudinal axis of the catheter shaft(1510) and/or inflatable member (1540).

In some embodiments, the ablation device (1500) is useful for forminglesions on endocardial surfaces via focal ablation, such as an innersurface of a ventricle. During use, the electrodes (1520, 1530, 1532,1534) may be disposed in a ventricle in order to deliver a pulsewaveform to ablate tissue, as described in more detail herein. A distalportion of the inflatable member (1540) may include and/or be formed inan atraumatic shape that reduces trauma to tissue. The catheter shaft(1510) and inflatable member (1540) may be sized for advancement into anendocardial space (e.g., left ventricle). The catheter shaft (1510) maybe flexible so as to be deflectable. For example, a deflectable portionof the catheter shaft (1510) may be configured for deflecting a portionof the catheter (1500) including the second set of electrodes (1530,1532, 1534) and the inflatable member (1540) up to about 210 degreesrelative to the longitudinal axis. The inflatable member (1540) may beconfigured to transition between a first configuration (e.g., deflatedstate) and a second configuration (e.g., inflated state). In the firstconfiguration, the inflatable member (1540) may have a diameter that isabout the same as a diameter of the catheter shaft (1510) to aid inadvancing the ablation device (1500) through vasculature. For example,the inflatable member (1540) in the first configuration may beapproximately parallel to a longitudinal axis of the catheter shaft(1510). The inflatable member (1540) when inflated may bias away fromthe longitudinal axis. The first set of electrodes (1520) may bestructurally and/or functionally similar to the electrodes (220, 230)described with respect to FIGS. 2A-2D.

The first set of electrodes (1520) may be electrically coupled togetherusing one or more electrical leads. The proximal electrodes (1534) ofthe second set of electrodes and the distal electrodes (1532, 1530) ofthe second set of electrodes may be electrically wired respectivelyseparately using different sets of electrical leads. In someembodiments, the first set of electrodes (1520) may be configured as ananode while the second set of electrodes (1530, 1532, 1534) may beconfigured as a cathode, or vice versa. In alternate embodiments, thefirst set of electrodes (1520) and the proximal electrodes (1534) of thesecond set of electrodes may be configured as an anode while the distalelectrodes (1532, 1530) of the second set of electrodes may beconfigured as a cathode, or vice versa. For example, the proximalelectrodes (1534) of the second set of electrodes, the distal electrodes(1532, 1530) of the second set of electrodes, and the first set ofelectrodes (1520) may each couple to respective insulated electricalleads, with each lead having sufficient electrical insulation to sustainan electrical potential difference of at least 700 V across itsthickness without dielectric breakdown.

The first and second sets of electrodes (1520, 1530, 1532, 1534) mayinclude an atraumatic shape to reduce trauma to tissue. For example, thefirst set of electrodes (1520) may be ring electrodes. In someembodiments, the first set of electrodes (1520) may be located along anyportion of the catheter shaft (1510) proximal to the second set ofelectrodes (1530, 1532, 1534). The first set of electrodes (1520) may bespaced apart from each other and wired together via one or moreinsulated leads so as to function as a single electrode (e.g., anode orcathode) while allowing the catheter shaft (1510) to remain flexible andfacilitate deflection. The second set of electrodes (1530, 1532, 1534)may be disposed on a surface of the inflatable member (1540) and/orflush with the surface of the inflatable member (1540). The second setof electrodes (1530, 1532) may have the same or different sizes, shapes,and/or location along the inflatable member (1540).

For example, the second set of electrodes (1530, 1532, 1534) may includea distal tip electrode (1530) and a set of generally elliptically-shapedelectrodes (1532, 1534) disposed around a circumference of theinflatable member (1540). In some embodiments, a major axis (e.g.,longitudinal axis) of each of the electrodes (1532, 1534) may besubstantially parallel to the longitudinal axis of the catheter shaft(1510) and/or inflatable member (1540). In some embodiments, the distaltip electrode (1532) may be electrically isolated from the first set ofelectrodes (1520). In some embodiments, each electrode of the second setof electrodes (1530, 1532, 1534) may be independently addressable. Thedistal tip electrode (1530) may be formed at a distal portion of theinflatable member (1540) and electrically isolated from the first set ofelectrodes (1520).

In some embodiments, a set of the second set of electrodes may beelectrically coupled with the first set of electrodes. For example, thefirst set of electrodes (1520) and the proximal electrodes (1534) of thesecond set of electrodes may be electrically coupled together using oneor more electrical leads. In some embodiments, the proximal electrodes(1534) may be formed proximal to a maximum cross-sectional diameter ofthe inflatable member (1540) when inflated. That is, a proximal portionof the inflatable member (1540) is proximal to a cross-sectionaldiameter of the inflatable member (1540) at its largest portion. In thisconfiguration the distal electrodes (1530, 1532) of the second set ofelectrodes may be configured to contact tissue in the secondconfiguration while the first set of electrodes (1520) and the proximalelectrodes (1534) of the second set of electrodes may be configured fornon-contact with tissue in the second configuration.

In some embodiments, one or more of the electrodes of the first andsecond sets of electrodes (1520, 1530, 1532, 1534) may be configured forreceiving or sensing an ECG signal for recording electrophysiology data.The ablation device (1500) may include one or more ECG signalelectrodes. For example, one or more electrodes of the second set ofelectrodes (1530, 1532, 1534) may be configured to receive an ECGsignal. These ECG signal electrodes, such as the distal tip electrode(1530), may be coupled to its own insulated electrical lead. In theseembodiments, the ablation device may be used to record electrophysiologydata in place of a mapping catheter before and/or after tissue ablation.

The inflatable member (1540) when inflated may have an asymmetric shapein a proximal-to-distal direction, so that one end (for example thedistal end) of the inflatable member (1540) is more bulbous than theother end (for example the proximal end) of the inflatable member(1540). The inflatable member (1540) when inflated may be rotationallysymmetric about the longitudinal axis of the catheter shaft (1510). Inthis configuration, the inflatable member (1540) may be placed at anendocardial surface and used to form a lesion via focal ablation (e.g.,a spot lesion). The electrode leads may be configured with sufficientinsulation and high dielectric strength to be suitable for delivery ofirreversible electroporation energy as described herein.

In some embodiments, the catheter shaft (1510) may include a deflectableportion between the first set of electrodes (1520) and the second set ofelectrodes (1530). In other embodiments the deflectable portion may beproximal to the first set of electrodes (1520). The deflectable portionmay be configured to deflect up to about 210 degrees relative to thelongitudinal axis of the catheter shaft (1510). In some embodiments, anactuator (e.g., fluid source) may be coupled to the inflatable memberand configured to transition the inflatable member between the firstconfiguration (e.g., deflated state) and the second configuration (e.g.,inflated state) by, for example, using pressurized saline.

In the embodiments described herein with respect to FIGS. 11-15, thefirst set of electrodes may be spaced apart from the second set ofelectrodes by between about 2 mm and about 10 mm. In some embodiments,the first set of electrodes may be formed on a portion of the cathetershaft having a length of between about 2 mm and about 12 mm. In someembodiments, the inflatable member when inflated may have a shape withan effective cross-sectional diameter at its largest portion of betweenabout 5 mm and about 15 mm. In some embodiments, the inflatable membermay have a length of up to about 22 mm. For example, the inflatablemember may have substantially the same length in the first configurationand the second configuration. In some embodiments, one or moreelectrodes of the first set of electrodes may have a width of betweenabout 1 mm and about 5 mm and may be spaced apart by between about 1 mmand about 5 mm. In some embodiments, a distal-most electrode of thefirst set of electrodes may be spaced apart by at least about 5 mm froma proximal end of the inflatable member when inflated.

II. Methods

Also described here are methods for ablating tissue in a heart chamberusing the systems and devices described above. The heart chamber mayinclude one or more of the right, left ventricle, and/or right, leftatria. Generally, the methods described here include introducing anddisposing a device in contact with one or more chambers such as theventricles. A pulse waveform may be delivered by one or more electrodesand an inflatable member (e.g., balloon) of the device to ablate tissue.In some embodiments, a cardiac pacing signal may synchronize thedelivered pulse waveforms with the cardiac cycle. Additionally oralternatively, the pulse waveforms may include a plurality of levels ofa hierarchy to reduce total energy delivery. The tissue ablation thusperformed may be delivered in synchrony with paced heartbeats and withless energy delivery to reduce damage to healthy tissue. It should beappreciated that any of the ablation devices described herein may beused to ablate tissue using the methods discussed below as appropriate.

In some embodiments, the ablation devices described herein may be usedfor focal ablation of cardiac features/structures identified to causearrhythmia. For example, a cardiac electrophysiology diagnostic catheter(e.g., mapping catheter) may be used to map cardiac structures such asre-entrant circuits and ventricular scar tissue that may be subsequentlyablated through focal ablation using any of the ablation devicesdescribed herein. Focal ablation may, for example, create a spot lesionthat neutralizes a re-entrant circuit while sparing surrounding tissue.In some embodiments, one or more focal ablation lesions may be formed incombination with one or more box or line lesions to treat cardiacarrhythmia. As a non-limiting example, in some embodiments, a system caninclude one or more mapping catheters, one or more ablation devices(e.g., as illustrated in FIGS. 2A-2C and 3) useful for creating lesionsvia focal ablation.

Generally, and as illustrated in FIGS. 4A-4B, a method (400) includesthe introduction of a device (e.g., ablation device, such as theablation devices (110, 200, 300, 500, 500′, 500″, 500″″, 1100, 1200,1300, 1400, 1500) into an endocardial space of a ventricle. The ablationdevice may be introduced in a first configuration and transitioned to asecond configuration in the ventricle. Once positioned in the ventricle,voltage pulse waveforms may be applied to tissue during a refractoryperiod of the cardiac cycle. Electrophysiology data of the ventricle maybe recorded to determine efficacy of the ablation.

The method (400) may begin with creating an access site in a patient(402). For example, to access the left ventricle for treatment, anantegrade delivery approach may be used, in which the first access sitemay be via a femoral vein of the patient. A guidewire may be advancedinto the access site via the femoral vein and into the right atrium ofthe patient (404). A dilator and a deflectable sheath may be advancedover the guidewire and into the right atrium (406). The sheath may, forexample, be configured for deflecting up to about 210 degrees. Thedilator may be advanced from the right atrium into the left atriumthrough the septum (408) to create a transseptal opening. For example,the dilator may be advanced from the right atrium into the left atriumthrough the interatrial septum to create the transseptal opening. Theinteratrial septum may include the fossa ovalis of the patient. Thetransseptal opening may be dilated using the dilator (410). For example,the dilator may be advanced out of the sheath and used to poke the fossaovalis to create the transseptal opening (assuming the patient isheparinized). Alternatively, a transseptal needle (e.g., Brockenbroughneedle) may be used to create the transseptal opening. The sheath may beadvanced from the right atrium into the left atrium (412) through thetransseptal opening. An ablation device may be advanced into the leftventricle over the guidewire (414) via the mitral valve. Alternatively,the left ventricle may be accessed by a retrograde approach, in whichthe first access site may be via a femoral artery of the patient, and aguidewire and ablation device may be advanced through an aorta of thepatient, and then through the aortic valve into the left ventricle. Fortreatment of the right ventricle, the first access site may again be viaa femoral vein of the patient, and the guidewire and ablation device maybe advanced into the right atrium of the patient and then through thetricuspid valve into the right ventricle.

In some embodiments, the ablation device may include a catheter shaftlumen and a set of insulated electrical leads extending through theshaft lumen. The catheter shaft may include one or more electrodesformed on a surface of the shaft. In some embodiments, one or moreelectrodes may be disposed on one or more portions of the inflatablemember. For example, an electrode may be disposed on a distal end of theinflatable member. One or more of the electrodes may be configured toreceive electrophysiology signals from the ventricle. In the method ofFIGS. 4A-4B, an ablation device may be configured to recordelectrophysiology data of the ventricle. In some embodiments, to allowthe ablation device to record electrophysiology data, the ablationdevice may be transitioned from the first configuration into the secondconfiguration (416) within the ventricle (e.g., left ventricle). In someembodiments, the inflatable member may be transitioned between the firstand second configurations using a handle of the ablation device. Forexample, the handle may include a saline flow control mechanism tocontrol a volume of saline within an inflatable member. The handle mayfurther include a saline volume indicator to indicate a configuration ofthe inflatable member. The ablation device in the second configurationmay be configured to record electrophysiology data using the ablationdevice (418). For example, one or more electrodes on the catheter shaftand inflatable member may be configured for receiving an ECG signal forrecording electrophysiology data.

In other embodiments, a separate diagnostic device (e.g., a mappingcatheter) may be used to record electrophysiology data of the ventricleto be treated. Electrophysiology data may be used to generate ananatomical map that may be used to compare electrophysiology datarecorded after energy delivery (e.g., ablation). The diagnostic devicemay be advanced into the selected ventricle via a femoral vein orjugular vein. In these embodiments, the diagnostic device (e.g., secondcatheter) may be advanced into the right ventricle (via the tricuspidvalve) or into the ventricle (via the left atrium and the mitral valve)over the guidewire after step (412) instead of advancing the ablationdevice into the selected ventricle. The second catheter may be used torecord electrophysiology data of one or more ventricles. Once completed,the diagnostic device may be withdrawn from the body over the guidewire,and the ablation device may then be advanced over the guidewire into theselected ventricle.

Still referring to FIGS. 4A-4B, a second access site may be created inthe patient to advance a lead or catheter for cardiac stimulation intothe patient's heart. For example, the second access site may be via ajugular vein of the patient. The device for cardiac stimulation may beadvanced into the right ventricle through the second access site (420)(e.g., near the apex of the right ventricle). A pacing signal may begenerated by a cardiac stimulator and applied to the heart for cardiacstimulation of the heart. An indication of the pacing signal may betransmitted from the cardiac stimulator to the signal generator. In someembodiments, the operator may confirm the pacing capture and determinethat the ventricle is responding to the pacing signal as intended. Forexample, pacing capture may be confirmed on an ECG display on a signalgenerator. Confirmation of pacing capture is a safety feature in thatablation is delivered in synchrony with pacing through enforcedperiodicity of a Q-wave through pacing.

The ablation device may be advanced towards a target ventricle (422) fordelivering a pulse waveform configured for tissue ablation. Inparticular, the ablation device in the second configuration may beadvanced towards a ventricle of the heart to contact a tissue surface.The sheath may be deflected as needed to direct the ablation devicetowards the target ventricle. The inflatable member may be transitionedto a second configuration where the inflatable member inflates tocontact the inflatable member against the ventricle at a predeterminedlocation. Once the ablation device is in position within the heart todeliver one or more pulse waveforms, an extension cable may be used toelectrically couple a signal generator to a proximal end of the handleof the ablation device. After pacing the right ventricle using thepacing device (424), the pulse waveform may be delivered to theventricle using the ablation device to ablate tissue in a portion of thetarget ventricle (426). The pulse waveform may be delivered insynchronization with the pacing signal.

As described in detail in the figures (e.g., FIGS. 5A-5J), the ablationdevice may be configured to generate an electric field intensity in aregion of myocardial tissue of a ventricle (e.g., where there may bere-entrant circuits, etc.) that is large enough to cause irreversibleelectroporation in tissue. For example, the inflatable member of theablation device in FIG. 5D may be in contact with a tissue surface andmay be used to generate a set of high intensity electric field linesthat penetrate the ventricle at a depth of between about 5 mm to about 8mm or more to form one or more focal ablation lesions, as shown by thespatial zone (532) in FIG. 5E. The ablation zone corresponding to thespatial region (532) may be wide and deep. The size of the inflatablemember may be modified to control a depth and strength of the electricfield. This allows energy to be delivered more efficiently and thuspermits tissue ablation with minimal total energy delivered.

While examples of ablation devices configured for delivery ofirreversible electroporation pulsed electric field therapy have beendescribed here, the examples described herein are provided for exemplarypurposes only and those skilled in the art may devise other variationswithout departing from the scope of the present invention. For example,a range and variety of materials, polyhedral sides, electrode diameters,device dimensions, voltage levels, proximal electrodes, and other suchdetails are possible and may be implemented as convenient for theapplication at hand without departing from the scope of the presentinvention. The catheter shaft may undergo a range of deflections bycontrolling deflection from a catheter handle. The metallized electrodeportions disposed on the inflatable member embodiments may be used forECG signal recording or irreversible electroporation therapy delivery orboth.

As discussed herein, the pulse waveform may be generated by a signalgenerator coupled to the ablation device. The signal generator may beelectrically coupled to a proximal end of a handle of the ablationdevice. For example, an extension cable may electrically couple thesignal generator to the proximal end of the handle. In some embodiments,the pulse waveform may include a time offset with respect to the pacingsignal. In some embodiments, the pulse waveform may include a firstlevel of a hierarchy of the pulse waveform including a first set ofpulses. Each pulse has a pulse time duration and a first time intervalseparating successive pulses. A second level of the hierarchy of thepulse waveform may include a plurality of first sets of pulses as asecond set of pulses. A second time interval may separate successivefirst sets of pulses. The second time interval may be at least threetimes the duration of the first time interval. A third level of thehierarchy of the pulse waveform may include a plurality of second setsof pulses as a third set of pulses. A third time interval may separatesuccessive second sets of pulses. The third time interval may be atleast thirty times the duration of the second level time interval. Afourth level of the hierarchy of the pulse waveform may include aplurality of third sets of pulses as a fourth set of pulses. A fourthtime interval may separate successive third sets of pulses. The fourthtime interval may be at least ten times the duration of the third leveltime interval.

One or more electrodes of the ablation device in the secondconfiguration may be configured to receive electrophysiology signals ofthe target ventricle and used to record electrophysiology data of thetarget ventricle (428). The electrophysiology data may be compared tothe baseline data recorded prior to ablation to determine if ablationwas successful (430).

In other embodiments, the ablation device may be withdrawn from theheart over the guidewire and a mapping catheter may be advanced over theguidewire to record the post-ablation electrophysiology data of thetarget ventricle. If the ablation is not successful (430—NO) based onthe electrophysiology data and predetermined criteria, then the processmay return to step 426 for delivery of additional pulse waveforms. Thepulse waveform parameters may be the same or changed for subsequentablation cycles.

If analysis of the electrophysiology data indicates that the ablation ofa ventricle portion is successful (e.g., tissue portion is electricallysilent) (430—YES), then a determination may be made of other targetventricle portions to ablate (432). Another target ventricle portion maybe selected (424) and the process may return to step 422 when otherventricular portions are to be ablated. When switching between targetventricles, the inflatable member may be at least partially deflated,and the ablation device may be advanced towards another portion oftissue. If no other portions are to be ablated (432—NO), the ablationdevice, cardiac stimulator, sheath, guidewire, and the like, may beremoved from the patient (436).

In other embodiments, the diagnostic device (e.g., mapping catheter) maybe used to record electrophysiology data of the ventricle after pulsewaveforms are delivered to tissue by the ablation device. In theseembodiments, the ablation device may be withdrawn from the patient overthe guidewire after steps 426 or 436 and the diagnostic device may beadvanced into the ventricle over the guidewire to recordelectrophysiology data of the target ventricle having undergone tissueablation.

It should be noted that for any of the steps described herein, aradiopaque portion of the ablation device may be fluoroscopically imagedto aid an operator. For example, visual confirmation may be performedthrough fluoroscopic imaging that the inflatable members in the secondconfiguration is in contact with the ventricle or to visually confirm anapposition of the inflatable member and electrodes relative to theventricle. Imaging from a plurality of angles may be used to confirmpositioning.

It should be understood that the examples and illustrations in thisdisclosure serve exemplary purposes and departures and variations suchas inflatable member characteristics, number of electrodes, and so oncan be built and deployed according to the teachings herein withoutdeparting from the scope of this invention.

Pulse Waveform

Disclosed herein are methods, systems and apparatuses for the selectiveand rapid application of pulsed electric fields/waveforms to effecttissue ablation with irreversible electroporation. The pulse waveform(s)as disclosed herein are usable with any of the systems (100), devices(e.g., 200, 300), and methods (e.g., 400) described herein. Someembodiments are directed to pulsed high voltage waveforms together witha sequenced delivery scheme for delivering energy to tissue via sets ofelectrodes. In some embodiments, peak electric field values can bereduced and/or minimized while at the same time sufficiently largeelectric field magnitudes can be maintained in regions where tissueablation is desired. In some embodiments, a system useful forirreversible electroporation includes a signal generator and a processorcapable of being configured to apply pulsed voltage waveforms to aselected plurality or a subset of electrodes of an ablation device. Insome embodiments, the processor is configured to control inputs wherebyselected pairs of anode-cathode subsets of electrodes can besequentially triggered based on a pre-determined sequence, and in oneembodiment the sequenced delivery can be triggered from a cardiacstimulator and/or pacing device. In some embodiments, the ablation pulsewaveforms are applied in a refractory period of the cardiac cycle so asto avoid disruption of the sinus rhythm of the heart. One example methodof enforcing this is to electrically pace the heart with a cardiacstimulator and ensure pacing capture to establish periodicity andpredictability of the cardiac cycle, and then to define a time windowwell within the refractory period of this periodic cycle within whichthe ablation waveform is delivered.

In some embodiments, the pulsed voltage waveforms disclosed herein arehierarchical in organization and have a nested structure. In someembodiments, the pulsed waveform includes hierarchical groupings ofpulses with a variety of associated timescales. Furthermore, theassociated timescales and pulse widths, and the numbers of pulses andhierarchical groupings, can be selected so as to satisfy one or more ofa set of Diophantine inequalities involving the frequency of cardiacpacing.

Pulsed waveforms for electroporation energy delivery as disclosed hereinmay enhance the safety, efficiency and effectiveness of the energydelivery by reducing the electric field threshold associated withirreversible electroporation, yielding more effective ablative lesionswith reduced total energy delivered. This in turn can broaden the areasof clinical application of electroporation including therapeutictreatment of a variety of cardiac arrhythmias.

FIG. 6 illustrates a pulsed voltage waveform in the form of a sequenceof rectangular double pulses, with each pulse, such as the pulse (600)being associated with a pulse width or duration. The pulsewidth/duration can be about 0.5 microseconds, about 1 microsecond, about5 microseconds, about 10 microseconds, about 25 microseconds, about 50microseconds, about 100 microseconds, about 125 microseconds, about 140microseconds, about 150 microseconds, including all values andsub-ranges in between. The pulsed waveform of FIG. 6 illustrates a setof monophasic pulses where the polarities of all the pulses are the same(all positive in FIG. 6, as measured from a zero baseline). In someembodiments, such as for irreversible electroporation applications, theheight of each pulse (600) or the voltage amplitude of the pulse (600)can be in the range from about 400 volts, about 1,000 volts, about 5,000volts, about 10,000 volts, about 15,000 volts, including all values andsub ranges in between. As illustrated in FIG. 6, the pulse (600) isseparated from a neighboring pulse by a time interval (602), alsosometimes referred to as a first time interval. The first time intervalcan be about 3 microseconds, about 50 microseconds, about 100microseconds, about 200 microseconds, about 500 microseconds, about 800microseconds, about 1 millisecond including all values and sub ranges inbetween, in order to generate irreversible electroporation.

FIG. 7 introduces a pulse waveform with the structure of a hierarchy ofnested pulses. FIG. 7 shows a series of monophasic pulses such as pulse(700) with pulse width/pulse time duration w, separated by a timeinterval (also sometimes referred to as a first time interval) such as(702) of duration t₁ between successive pulses, a number m₁ of which arearranged to form a group of pulses (710) (also sometimes referred to asa first set of pulses). Furthermore, the waveform has a number m₂ ofsuch groups of pulses (also sometimes referred to as a second set ofpulses) separated by a time interval (712) (also sometimes referred toas a second time interval) of duration t₂ between successive groups. Thecollection of m₂ such pulse groups, marked by (720) in FIG. 7,constitutes the next level of the hierarchy, which can be referred to asa packet and/or as a third set of pulses. The pulse width and the timeinterval t₁ between pulses can both be in the range of microseconds tohundreds of microseconds, including all values and sub ranges inbetween. In some embodiments, the time interval t₂ can be at least threetimes larger than the time interval t₁. In some embodiments, the ratiot₂/t₁ can be in the range between about 3 and about 300, including allvalues and sub-ranges in between.

FIG. 8 further elaborates the structure of a nested pulse hierarchywaveform. In this figure, a series of m₁ pulses (individual pulses notshown) form a group of pulses (800) (e.g., a first set of pulses). Aseries of m₂ such groups separated by an inter-group time interval (810)of duration t₂ (e.g., a second time interval) between one group and thenext form a packet (e.g., a second set of pulses). A series of m₃ suchpackets separated by time intervals (812) of duration t₃ (e.g., a thirdtime interval) between one packet and the next form the next level inthe hierarchy, a super-packet labeled (820) (e.g., a third set ofpulses) in the figure. In some embodiments, the time interval t₃ can beat least about thirty times larger than the time interval t₂. In someembodiments, the time interval t₃ can be at least fifty times largerthan the time interval t₂. In some embodiments, the ratio t₃/t₂ can bein the range between about 30 and about 800, including all values andsub-ranges in between. The amplitude of the individual voltage pulses inthe pulse hierarchy can be anywhere in the range from 500 volts to 7,000volts or higher, including all values and sub ranges in between.

FIG. 9 provides an example of a biphasic waveform sequence with ahierarchical structure. In the example shown in the figure, biphasicpulses such as (900) have a positive voltage portion as well as anegative voltage portion to complete one cycle of the pulse. There is atime delay (902) (e.g., a first time interval) between adjacent cyclesof duration t₁, and n₁ such cycles form a group of pulses (910) (e.g., afirst set of pulses). A series of n₂ such groups separated by aninter-group time interval (912) (e.g., a second time interval) ofduration t₂ between one group and the next form a packet (920) (e.g., asecond set of pulses). The figure also shows a second packet (930), witha time delay (932) (e.g., a third time interval) of duration t₃ betweenthe packets. Just as for monophasic pulses, higher levels of thehierarchical structure can be formed as well. The amplitude of eachpulse or the voltage amplitude of the biphasic pulse can be anywhere inthe range from 500 volts to 7,000 volts or higher, including all valuesand sub ranges in between. The pulse width/pulse time duration can be inthe range from nanoseconds or even sub-nanoseconds to tens ofmicroseconds, while the delays t₁ can be in the range from zero toseveral microseconds. The inter-group time interval t₂ can be at leastten times larger than the pulse width. In some embodiments, the timeinterval t₃ can be at least about twenty times larger than the timeinterval t₂. In some embodiments, the time interval t₃ can be at leastfifty times larger than the time interval t₂.

Embodiments disclosed herein include waveforms structured ashierarchical waveforms that include waveform elements/pulses at variouslevels of the hierarchy. The individual pulses such as (700) in FIG. 7comprise the first level of the hierarchy, and have an associated pulsetime duration and a first time interval between successive pulses. A setof pulses, or elements of the first level structure, form a second levelof the hierarchy such as the group of pulses/second set of pulses (710)in FIG. 7. Among other parameters, associated with the waveform areparameters such as a total time duration of the second set of pulses(not shown), a total number of first level elements/first set of pulses,and second time intervals between successive first level elements thatdescribe the second level structure/second set of pulses. In someembodiments, the total time duration of the second set of pulses can bebetween about 20 microseconds and about 10 milliseconds, including allvalues and subranges in between. A set of groups, second set of pulses,or elements of the second level structure, form a third level of thehierarchy such as the packet of groups/third set of pulses (720) in FIG.7. Among other parameters, there is a total time duration of the thirdset of pulses (not shown), a total number of second levelelements/second set of pulses, and third time intervals betweensuccessive second level elements that describe the third levelstructure/third set of pulses. In some embodiments, the total timeduration of the third set of pulses can be between about 60 microsecondsand about 200 milliseconds, including all values and sub ranges inbetween. The generally iterative or nested structure of the waveformscan continue to a higher plurality of levels, such as ten levels ofstructure, or more.

For example, a pulse waveform may include a fourth level of thehierarchy of the pulse waveform may include a plurality of third sets ofpulses as a fourth set of pulses, a fourth time interval separatingsuccessive third sets of pulses, the fourth time interval being at leastten times the duration of the third level time interval.

In some embodiments, hierarchical waveforms with a nested structure andhierarchy of time intervals as described herein are useful forirreversible electroporation ablation energy delivery, providing a gooddegree of control and selectivity for applications in different tissuetypes. A variety of hierarchical waveforms can be generated with asuitable pulse generator. It is understood that while the examplesherein identify separate monophasic and biphasic waveforms for clarity,it should be noted that combination waveforms, where some portions ofthe waveform hierarchy are monophasic while other portions are biphasic,can also be generated/implemented.

In some embodiments, the ablation pulse waveforms described herein areapplied during the refractory period of the cardiac cycle so as to avoiddisruption of the sinus rhythm of the heart. In some embodiments, amethod of treatment includes electrically pacing the heart with acardiac stimulator to ensure pacing capture to establish periodicity andpredictability of the cardiac cycle, and then defining a time windowwithin the refractory period of the cardiac cycle within which one ormore pulsed ablation waveforms can be delivered. FIG. 10 illustrates anexample where both atrial and ventricular pacing is applied (forinstance, with pacing leads or catheters situated in the right atriumand right ventricle respectively). With time represented on thehorizontal axis, FIG. 10 illustrates a series of ventricular pacingsignals such as (1000) and (1010), and a series of atrial pacing signals(1020, 1030), along with a series of ECG waveforms (1040, 1042) that aredriven by the pacing signals. As indicated in FIG. 10 by the thickarrows, there is an atrial refractory time window (1022) and aventricular refractory time window (1002) that respectively follow theatrial pacing signal (1022) and the ventricular pacing signal (1000). Asshown in FIG. 10, a common refractory time window (1050) of durationT_(r) can be defined that lies within both atrial and ventricularrefractory time windows (1022, 1002). In some embodiments, theelectroporation ablation waveform(s) can be applied in this commonrefractory time window (1050). The start of this refractory time window(1022) is offset from the pacing signal (1000) by a time offset (1004)as indicated in FIG. 10. The time offset (1004) can be smaller thanabout 25 milliseconds, in some embodiments. At the next heartbeat, asimilarly defined common refractory time window (1052) is the next timewindow available for application of the ablation waveform(s). In thismanner, the ablation waveform(s) may be applied over a series ofheartbeats, at each heartbeat remaining within the common refractorytime window. In one embodiment, each packet of pulses as defined abovein the pulse waveform hierarchy can be applied over a heartbeat, so thata series of packets is applied over a series of heartbeats, for a givenelectrode set.

As used herein, the terms “about” and/or “approximately” when used inconjunction with numerical values and/or ranges generally refer to thosenumerical values and/or ranges near to a recited numerical value and/orrange. In some instances, the terms “about” and “approximately” may meanwithin ±10% of the recited value. For example, in some instances, “about100 [units]” may mean within ±10% of 100 (e.g., from 90 to 110). Theterms “about” and “approximately” may be used interchangeably.

Some embodiments described herein relate to a computer storage productwith a non-transitory computer-readable medium (also may be referred toas a non-transitory processor-readable medium) having instructions orcomputer code thereon for performing various computer-implementedoperations. The computer-readable medium (or processor-readable medium)is non-transitory in the sense that it does not include transitorypropagating signals per se (e.g., a propagating electromagnetic wavecarrying information on a transmission medium such as space or a cable).The media and computer code (also may be referred to as code oralgorithm) may be those designed and constructed for the specificpurpose or purposes. Examples of non-transitory computer-readable mediainclude, but are not limited to, magnetic storage media such as harddisks, floppy disks, and magnetic tape; optical storage media such asCompact Disc/Digital Video Discs (CD/DVDs), Compact Disc-Read OnlyMemories (CD-ROMs), and holographic devices; magneto-optical storagemedia such as optical disks; carrier wave signal processing modules; andhardware devices that are specially configured to store and executeprogram code, such as Application-Specific Integrated Circuits (ASICs),Programmable Logic Devices (PLDs), Read-Only Memory (ROM) andRandom-Access Memory (RAM) devices. Other embodiments described hereinrelate to a computer program product, which may include, for example,the instructions and/or computer code disclosed herein.

The systems, devices, and/or methods described herein may be performedby software (executed on hardware), hardware, or a combination thereof.Hardware modules may include, for example, a general-purpose processor(or microprocessor or microcontroller), a field programmable gate array(FPGA), and/or an application specific integrated circuit (ASIC).Software modules (executed on hardware) may be expressed in a variety ofsoftware languages (e.g., computer code), including C, C++, Java®, Ruby,Visual Basic®, and/or other object-oriented, procedural, or otherprogramming language and development tools. Examples of computer codeinclude, but are not limited to, micro-code or micro-instructions,machine instructions, such as produced by a compiler, code used toproduce a web service, and files containing higher-level instructionsthat are executed by a computer using an interpreter. Additionalexamples of computer code include, but are not limited to, controlsignals, encrypted code, and compressed code.

The specific examples and descriptions herein are exemplary in natureand embodiments may be developed by those skilled in the art based onthe material taught herein without departing from the scope of thepresent invention, which is limited only by the attached claims.

We claim:
 1. An apparatus, comprising: a catheter shaft defining alongitudinal axis; an inflatable member coupled to a distal end of thecatheter shaft; a first electrode formed on a needle configured to atleast partially extend from a distal end of the inflatable member, theneedle configured to penetrate into tissue; and a second electrodeformed on the inflatable member and electrically isolated from the firstelectrode, the first electrode and the second electrode configured tohave opposite polarities during delivery of a pulse waveform such thatthe first electrode and the second electrode collectively generate anelectric field that ablates the tissue around the needle.
 2. Theapparatus of claim 1, wherein the second electrode is formed on theinflatable member on an approximate plane approximately perpendicular tothe longitudinal axis.
 3. The apparatus of claim 1, wherein the firstelectrode and the second electrode has an insulated electrical leadassociated therewith, the insulated electrical lead configured forsustaining a voltage potential of at least about 700 V withoutdielectric breakdown of its corresponding insulation, the insulatedelectrical lead disposed in a lumen of the catheter shaft.
 4. Theapparatus of claim 1, wherein the first electrode is formed on a portionof the needle having a length of at least about 8 mm.
 5. The apparatusof claim 1, wherein the first electrode is spaced apart by at leastabout 5 mm from a proximal end of the inflatable member.
 6. Theapparatus of claim 1, wherein the first electrode is formed on a portionof the needle having a length of at least about 8 mm.
 7. The apparatusas in claim 1, wherein a distal end of the inflatable member has aconcave surface on its outside, wherein the second electrode is formedon the concave surface.
 8. The apparatus of claim 1, wherein theinflatable member is transitionable between a first configuration and asecond configuration, the inflatable member in the second configurationhaving a cross-sectional diameter at its largest portion of betweenabout 6 mm and about 22 mm.
 9. The apparatus of claim 1, wherein theinflatable member has an annular profile with a planar distal end, andthe second electrode is disposed on the planar distal end of theinflatable member.
 10. The apparatus of claim 9, wherein the secondelectrode extends across the planar distal end of the inflatable member.11. The apparatus of claim 1, wherein the needle is deployable in thelongitudinal direction.
 12. An apparatus, comprising: a catheter shaftdefining a longitudinal axis; an annular inflatable member coupled to adistal end of the catheter shaft, the annular inflatable member defininga lumen therethrough; a first electrode disposed on a distal end of theannular inflatable member, the first electrode having a substantiallyplanar portion; and a second electrode having a needle shape, the secondelectrode configured to at least partially extend from, and distal to,the lumen and the first electrode and being spaced apart from the firstelectrode, the second electrode configured to penetrate into tissue, thefirst and second electrodes configured to have opposite polaritiesduring delivery of a pulse waveform such that the first and secondelectrodes collectively generate an electric field that ablates thetissue around the needle.
 13. The apparatus of claim 12, wherein theannular inflatable member is transitionable between a firstconfiguration and a second configuration, the annular inflatable memberin the second configuration has a diameter of between about 10 mm andabout 15 mm.
 14. The apparatus of claim 12, wherein the second electrodeis deployable from a configuration in which the second electrode issubstantially within the lumen of the inflatable member to aconfiguration in which the second electrode at least partially extendsdistal to the distal end of the lumen of the inflatable member.